Antibodies targeting il-18 receptor beta (il-18rΒ) and related methods

Abstract

Provided are novel antibodies and antigen-binding fragments thereof that bind interleukin-18 receptor beta (IL-18RP), along with conjugates thereof, nucleic acids encoding the same, compositions comprising the same, and methods of producing and using the same, including in the treatment of various diseases and conditions, such as inflammatory bowel disease, and other immune-mediated diseases, autoimmune diseases, inflammatory diseases, cancers, and infectious diseases.

Description

ANTIBODIES TARGETING IL-18 RECEPTOR BETA (IL-18Rβ) AND RELATED METHODSCross-Reference to Related Applications[1] This application claims priority to U.S. Provisional Application No. 63 / 612,973, filed December 20, 2023, and U.S. Provisional Application No. 63 / 645,496, filed May 10, 2024, each entitled “ANTIBODIES TARGETING IL-18 RECEPTOR BETA (IL-18RB) AND RELATED METHODS,” the contents of which is incorporated by reference in their entireties.Reference to An Electronic Sequence Listing[2] The present application is being filed with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled 735042028340SeqList.xml, created on December 10, 2024, which is 247,740 bytes in size. The information in the electronic format of the Sequence Listing is incorporated by reference in its entirety.Field[3] The present disclosure provides novel antibodies and antigen-binding fragments thereof that bind interleukin-18 receptor beta (IL-18Rβ), along with conjugates thereof, nucleic acids encoding the same, compositions comprising the same, and methods of producing and using the same, including in the treatment of various diseases and conditions, such as inflammatory bowel disease. Background[4] IL-18 is a member of the IL-1 family of cytokines, and plays an important role in the activation of immune responses, including both Th1 and Th2 responses, in a variety of diseases. Thus, there is a need for targeting the IL-18 signaling pathway for treatment of such diseases. However, current treatment options have not been met with success. For instance, a large proportion of inflammatory bowel disease patients do not achieve remission with standard-of-care therapies. Embodiments provided herein address these needs.Summary[5] Provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 8, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 9, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 10; and the VL region comprises a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24.[6] Also provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 34; and the VL region comprises a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 35.[7] Also provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 8, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 9, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 10; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 22, a light chain complementarity determining region 2 (CDR-L2) comprising the amino acid sequence of SEQ ID NO: 36, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24.[8] Also provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 34; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 35.[9] In some of any of such embodiments, the VH region is or comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 34.

[10] In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 35.

[11] In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 35.

[12] In some of any of such embodiments, the VH region comprises the amino acid sequence of SEQ ID NO: 34. In some of any of such embodiments, the VL region comprises the amino acid sequence of SEQ ID NO: 35. In some of any of such embodiments, the VH region comprises the amino acid sequence of SEQ ID NO: 34; and the VL region comprises the amino acid sequence of SEQ ID NO: 35.

[13] In some of any of such embodiments, the antibody or antigen-binding fragment thereof is an antibody comprising a constant domain. In some of any of such embodiments, the constant domain is a constant domain selected from the group consisting of an IgA1 constant domain, an IgA2 constant domain, an IgD constant domain, an IgE constant domain, an IgG1 constant domain, an IgG2 constant domain, an IgG3 constant domain, an IgG4 constant domain, and an IgM constant domain. In some of any of such embodiments, the constant domain is an IgG1 constant domain.

[14] In some of any of such embodiments, the antibody comprises: a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 30, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain constant domain comprising the amino acid sequence of SEQ ID NO: 31, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31. In some of any of such embodiments, the antibody comprises a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 30, and a light chain constant domain comprising the amino acid sequence of SEQ ID NO: 31.

[15] In some of any of such embodiments, the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 32, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; and a light chain comprising the amino acid sequence of SEQ ID NO: 33, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some of any of such embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32, and a light chain comprising the amino acid sequence of SEQ ID NO: 33.

[16] Also provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 52, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 53, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 54; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 66, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 67, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 68.

[17] Also provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 75; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 76.

[18] In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 75.

[19] In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some of any of such embodiments, the VL region comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 76.

[20] In some of any of such embodiments, the VH region comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 76.

[21] In some of any of such embodiments, the VH region comprises the amino acid sequence of SEQ ID NO: 75. In some of any of such embodiments, the VL region comprises the amino acid sequence of SEQ ID NO: 76. In some of any of such embodiments, the VH region comprises the amino acid sequence of SEQ ID NO: 75; and the VL region comprises the amino acid sequence of SEQ ID NO: 76.

[22] In some of any of such embodiments, the antibody or antigen-binding fragment thereof is an antibody comprising a constant domain. In some of any of such embodiments, the constant domain is a constant domain selected from the group consisting of an IgA1 constant domain, an IgA2 constant domain, an IgD constant domain, an IgE constant domain, an IgG1 constant domain, an IgG2 constant domain, an IgG3 constant domain, an IgG4 constant domain, and an IgM constant domain. In some of any of such embodiments, the constant domain is an IgG1 constant domain.

[23] In some of any of such embodiments, the antibody comprises: a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 30, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and a light chain constant domain comprising the amino acid sequence of SEQ ID NO: 31, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31. In some of any of such embodiments, the antibody comprises a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 30, and a light chain constant domain comprising the amino acid sequence of SEQ ID NO: 31.

[24] In some of any of such embodiments, the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 73; and a light chain comprising the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 74.

[25] In some of any of such embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 73, and a light chain comprising the amino acid sequence of SEQ ID NO: 74.

[26] In some of any of such embodiments, the antibody or antigen-binding fragment thereof is an antigen-binding fragment. In some of any of such embodiments, the antigen-binding fragment is selected from the group consisting of a single domain antibody, a single chain antibody, an unibody, a single chain variable fragment (scFv), a Fab fragment, and a F(ab')2 fragment.

[27] In some of any of such embodiments, the antibody or antigen-binding fragment thereof is recombinant. In some of any of such embodiments, the antibody or antigen-binding fragment thereof is monoclonal. In some of any of such embodiments, the antibody or antigen-binding fragment thereof is human.

[28] In some of any of such embodiments, the antibody or antigen-binding fragment thereof binds to human IL-18Rβ at pH 7.4 with an equilibrium dissociation constant (KD) that is about 1.5nM or is less than about 1.5 nM. In some of any of such embodiments, the antibody or antigen-binding fragment thereof binds to cynomolgus IL-18Rβ at pH 7.4 with an equilibrium dissociation constant (KD) that is about 2nM or is less than about 2 nM. In some of any of such embodiments, the antibody or antigen-binding fragment thereof binds to human IL-18Rβ at pH 7.4 with an equilibrium dissociation constant (KD) that is, is about, is less than, or is less than about 2 nM. In some of any of such embodiments, the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of 0.33 to 3.33, or about 0.33 to about 3.33. In some of any of such embodiments, the KD ratio is 0.8 to 1.3, or about 0.8 to about 1.3.

[29] In some of any of such embodiments, the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of 0.25 to 1.00, or about 0.25 to about 1.00. In some of any of such embodiments, the KD ratio is 0.25 to 0.5, or about 0.25 to about 0.5.

[30] In some of any of such embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof binds to an epitope of human IL-18Rβ that comprises, consists essentially of, or consists of residues 242-248, 279, 281, 282, 312, 342, and 343, with residue numbering corresponding to the amino acid sequence of SEQ ID NO: 126.

[31] In some of any of such embodiments, the human IL-18Rβ comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 126.

[32] In some of any of such embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof blocks IL-18Rβ binding to an IL-18 / IL-18Rα complex.

[33] In some of any of such embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises at least one post-translational modification of the amino acid sequence, optionally wherein the at least one post-translational modification comprises a post-translational modification of a heavy chain N-terminal glutamine (Q) to a pyroglutamate.

[34] Also provided herein is a multi-specific antibody, comprising a first antigen-binding domain that binds to IL-18Rβ and a second antigen-binding domain that binds to a second antigen, wherein the first antigen-binding domain comprises any anti-IL-18Rβ antibody or antigen-binding fragment thereof disclosed herein. In some embodiments, the multi-specific antibody is a bispecific antibody.

[35] Also provided herein is a conjugate, comprising any anti-IL-18Rβ antibody or antigen-binding fragment thereof disclosed herein, or any multi-specific antibody disclosed herein, and a heterologous molecule or moiety.

[36] Also provided herein is a polynucleotide comprising a nucleic acid(s) encoding any anti-IL-18Rβ antibody or antigen-binding fragment thereof disclosed herein, or a heavy chain or a light chain thereof.

[37] Also provided herein is a nucleic acid(s) encoding any anti-IL-18Rβ antibody or antigen-binding fragment thereof disclosed herein, or a heavy chain or a light chain thereof.

[38] In some embodiments, the nucleic acid(s) comprises a nucleic acid encoding a VH region comprising the nucleotide sequence of SEQ ID NO: 127 or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 127; and a nucleic acid encoding a VL region comprising the nucleotide sequence of SEQ ID NO: 128, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 128. In some embodiments, the nucleic acid(s) comprises a nucleic acid encoding a VH region comprising the nucleotide sequence of SEQ ID NO: 127; and a nucleic acid encoding a VL region comprising the nucleotide sequence of SEQ ID NO: 128. In some embodiments, the nucleic acid(s) comprises a nucleic acid encoding a heavy chain comprising the nucleotide sequence of SEQ ID NO: 129, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 129; and a nucleic acid encoding a light chain comprising the nucleotide sequence of SEQ ID NO: 130, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 130. In some embodiments, the nucleic acid(s) comprises a nucleic acid encoding a heavy chain comprising the nucleotide sequence of SEQ ID NO: 129; and a nucleic acid encoding a light chain comprising the nucleotide sequence of SEQ ID NO: 130.

[39] In some embodiments, the nucleic acid(s) comprises a nucleic acid encoding a VH region comprising the nucleotide sequence of SEQ ID NO: 131, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 131; and a nucleic acid encoding a VL region comprising the nucleotide sequence of SEQ ID NO: 132, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 132. In some embodiments, the nucleic acid(s) comprises a nucleic acid encoding a VH region comprising the nucleotide sequence of SEQ ID NO: 131; and a nucleic acid encoding a VL region comprising the nucleotide sequence of SEQ ID NO: 132. In some embodiments, the nucleic acid(s) comprises a nucleic acid encoding a heavy chain comprising the nucleotide sequence of SEQ ID NO: 133, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 133; and a nucleic acid encoding a light chain comprising the nucleotide sequence of SEQ ID NO: 134, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 134. In some embodiments, the nucleic acid(s) comprises a nucleic acid encoding a heavy chain comprising the nucleotide sequence of SEQ ID NO: 133; and a nucleic acid encoding a light chain comprising the nucleotide sequence of SEQ ID NO: 134.

[40] Also provided herein is a vector, comprising any polynucleotide or any nucleic acid(s) disclosed herein. In some embodiments, the vector is a viral vector. In some embodiments, the viral vector is a retroviral vector or a lentiviral vector.

[41] Also provided herein is a host cell comprising any anti-IL-18Rβ antibody or antigen-binding fragment thereof disclosed herein, any polynucleotide disclosed herein, any nucleic acid(s) disclosed herein, or any vector disclosed herein.

[42] Also provided herein is a method of producing an antibody or antigen-binding fragment thereof comprising culturing any host cell disclosed herein under a condition that produces the antibody or antigen-binding fragment thereof. In some embodiments, the method further comprises recovering the antibody or antigen-binding fragment thereof produced by the host cell.

[43] Also provided herein is an antibody or antigen-binding fragment thereof produced by any method of production disclosed herein.

[44] Also provided herein is a composition comprising any anti-IL-18Rβ antibody or antigen-binding fragment thereof disclosed herein, any multi-specific antibody disclosed herein, or any conjugate disclosed herein.

[45] In some of embodiments, the composition further comprises a pharmaceutically acceptable excipient.

[46] Also provided herein is a method of treatment, comprising administering any anti-IL-18Rβ antibody or antigen-binding fragment thereof disclosed herein, any multi-specific antibody disclosed herein, any conjugate disclosed herein, or any composition disclosed herein, to a subject having a disease or disorder.

[47] In some embodiments, the method of treatment further comprises administering one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents comprises, consists essentially of, or consists of an aminosalicylate, a corticosteroid, a thiopurine, a methotrexate, a tumor necrosis factor (TNF) inhibitor, an α4β7 integrin inhibitor, a TNF-α inhibitor, an IL-23 inhibitor, a dual IL-12 and IL-23 inhibitor, a tumor necrosis factor-like cytokine 1A (TL1A) inhibitor, an IL-2-CD25 fusion protein, a bispecific anti-TL1A / anti-TNF-α binding protein, an E-type prostanoid receptor 4 (EP4) agonist, a TYK2 inhibitor, a sphingosine-1-phosphate receptor (S1PR) agonist, a Janus kinase (JAK) inhibitor, an interkeukin-1 receptor associated kinase 4 (IRAK-4) inhibitor, a toll-like receptor 7 and 8 (TLR7 / 8) inhibitor, or an IL-22 inhibitor.

[48] In some of any of such embodiments, the one or more additional therapeutic agents is administered concurrently with the anti-IL-18Rβ antibody or antigen-binding fragment thereof, the multi-specific antibody, the conjugate, or the composition. In some of any of such embodiments, the one or more additional therapeutic agents is administered before or after the anti-IL-18Rβ antibody or antigen-binding fragment thereof, the multi-specific antibody, the conjugate, or the composition.

[49] In some of any of such embodiments, the disease or disorder is an immune-mediated disease, an autoimmune disease, an inflammatory disease, a cancer, or an infectious disease. In some of any of such embodiments, the disease or disorder is associated with an increase in IL-18Rβ in a biological sample of the subject as compared to a subject not having the disease or disorder. In some embodiments, the biological sample is a serum sample.

[50] In some of any of such embodiments, the disease or disorder is an immune-mediated disease. In some of any of such embodiments, the disease or disorder is an inflammatory disease. In some of any of such embodiments, the disease or disorder is an inflammatory bowel disease. In some embodiments, the inflammatory bowel disease is Crohn’s disease. In some embodiments, the inflammatory bowel disease is ulcerative colitis. In some of any of such embodiments, the disease or disorder is chronic obstructive pulmonary disease (COPD). In some of any of such embodiments, the disease or disorder is an autoimmune disease. In some of any of such embodiments, the disease or disorder is a cancer. In some of any of such embodiments, the disease or disorder is an infectious disease.

[51] In some of any of such embodiments, the disease or disorder is inflammatory bowel disease, chronic obstructive pulmonary disease (COPD), type 1 diabetes, type 2 diabetes, liver disease, organ transplant rejection, multiple sclerosis, arthritis, psoriasis, heart disease, macrophage activation syndrome (MAS), adult-onset Still’s disease (AOSD), hemophagocytic lymphohistiocytosis (HLH), dry eye disease (DED), cytokine release syndrome (CRS), systemic inflammatory response syndrome SIRS), autoinflammation with infantile enterocolitis (AIFEC), XIAP deficiency, NLRC4 gain-of-function mutation, sarcoidosis, atopic dermatitis, Behçet’s disease, systemic lupus erythematosus (SLE), acute coronary syndrome, allergies, amyotrophic lateral sclerosis (ALS), asthma, Celiac disease, or age-related macular degeneration (AMD), osteoporosis, Parkinson’s disease, Grave’s disease, Hashimoto’s thyroiditis, Addison’s disease, dermatomyositis, myasthenia gravis, pernicious anemia, Sjogren syndrome, vasculitis, uveitis, sepsis, atherosclerosis, ankylosing spondylitis, acute respiratory syndrome coronavirus (SARS-CoV), or acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

[52] In some of any of such embodiments: the inflammatory bowel disease is Crohn’s disease or ulcerative colitis; the arthritis is rheumatoid arthritis, psoriatic arthritis, idiopathic arthritis, or giant cell arthritis; the psoriasis is plaque psoriasis; the organ transplant rejection is a kidney transplant rejection; the heart disease is ischemic heart disease; the MAS is infantile MAS; or the sarcoidosis is pulmonary sarcoidosis. In some of any of such embodiments: the rheumatoid arthritis is juvenile rheumatoid arthritis; or the idiopathic arthritis is juvenile idiopathic arthritis.

[53] In some of any of such embodiments, the subject is a human.

[54] Also provided herein is a use of any composition disclosed herein for the manufacture of a medicament for treatment of a disease or disorder.

[55] Also provided herein is a use of any composition disclosed herein for treatment of a disease or disorder.

[56] Also provided herein is any composition disclosed herein for use in treatment of a disease or disorder.

[57] In some of any of such embodiments, the treatment further comprises administering one or more additional therapeutic agents. In some of any of such embodiments, the one or more additional therapeutic agents comprises, consists essentially of, or consists of an aminosalicylate, a corticosteroid, a thiopurine, a methotrexate, a tumor necrosis factor (TNF) inhibitor, an α4β7 integrin inhibitor, a TNF-α inhibitor, an IL-23 inhibitor, a dual IL-12 and IL-23 inhibitor, a tumor necrosis factor-like cytokine 1A (TL1A) inhibitor, an IL-2-CD25 fusion protein, a bispecific anti-TL1A / anti-TNF-α binding protein, an E-type prostanoid receptor 4 (EP4) agonist, a TYK2 inhibitor, a sphingosine-1-phosphate receptor (S1PR) agonist, a Janus kinase (JAK) inhibitor, an interkeukin-1 receptor associated kinase 4 (IRAK-4) inhibitor, a toll-like receptor 7 and 8 (TLR7 / 8) inhibitor, or an IL-22 inhibitor.

[58] In some of any of such embodiments, the one or more additional therapeutic agents is to be administered concurrently with the anti-IL-18Rβ antibody or antigen-binding fragment thereof, the multi-specific antibody, the conjugate, or the composition. In some of any of such embodiments, the one or more additional therapeutic agents is to be administered sequentially with the anti-IL-18Rβ antibody or antigen-binding fragment thereof, the multi-specific antibody, the conjugate, or the composition.

[59] In some of any of such embodiments, the disease or disorder is an immune-mediated disease, an autoimmune disease, an inflammatory disease, a cancer, or an infectious disease. In some of any of such embodiments, the disease or disorder is an immune-mediated disease. In some of any of such embodiments, the disease or disorder is an inflammatory disease. In some of any of such embodiments, the disease or disorder is an inflammatory bowel disease. In some of any of such embodiments, the inflammatory bowel disease is Crohn’s disease. In some of any of such embodiments, the inflammatory bowel disease is ulcerative colitis. In some of any of such embodiments, the disease or disorder is chronic obstructive pulmonary disease (COPD). In some of any of such embodiments, the disease or disorder is an autoimmune disease. In some of any of such embodiments, the disease or disorder is a cancer. In some of any of such embodiments, the disease or disorder is an infectious disease.

[60] In some of any of such embodiments, the disease or disorder is inflammatory bowel disease, allergy, chronic obstructive pulmonary disease (COPD), type 1 diabetes, type 2 diabetes, liver disease, organ transplant rejection, multiple sclerosis, arthritis, psoriasis, heart disease, macrophage activation syndrome (MAS), adult-onset Still’s disease (AOSD), hemophagocytic lymphohistiocytosis (HLH), dry eye disease (DED), cytokine release syndrome (CRS), systemic inflammatory response syndrome SIRS), autoinflammation with infantile enterocolitis (AIFEC), XIAP deficiency, NLRC4 gain-of-function mutation, sarcoidosis, atopic dermatitis, Behçet’s disease, systemic lupus erythematosus (SLE), acute coronary syndrome, allergies, amyotrophic lateral sclerosis (ALS), asthma, Celiac disease, or age-related macular degeneration (AMD), osteoporosis, Parkinson’s disease, Grave’s disease, Hashimoto’s thyroiditis, Addison’s disease, dermatomyositis, myasthenia gravis, pernicious anemia, Sjogren syndrome, vasculitis, uveitis, sepsis, atherosclerosis, ankylosing spondylitis, acute respiratory syndrome coronavirus (SARS-CoV), or acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

[61] In some of any of such embodiments: the inflammatory bowel disease is Crohn’s disease or ulcerative colitis; the arthritis is rheumatoid arthritis, psoriatic arthritis, idiopathic arthritis, or giant cell arthritis; the psoriasis is plaque psoriasis; the organ transplant rejection is a kidney transplant rejection; the heart disease is ischemic heart disease; the MAS is infantile MAS; or the sarcoidosis is pulmonary sarcoidosis. In some of any of such embodiments: the rheumatoid arthritis is juvenile rheumatoid arthritis; or the idiopathic arthritis is juvenile idiopathic arthritis.Brief Description of the Drawings

[62] FIG. 1 shows a human IL-18Rβ LSA binding sensorgram overlay for one panel of candidate α-human IL-18Rβ antibodies.

[63] FIG. 2 shows an isoaffinity plot for LSA screening of candidate α-IL-18Rβ antibodies.

[64] FIG. 3 shows a human IL-18Rβ isoaffinity plot for Biacore 8K screening of candidate α-IL-18Rβ antibodies.

[65] FIG. 4 shows a cynomolgus monkey IL-18Rβ isoaffinity plot for Biacore 8K screening of candidate α-IL-18Rβ antibodies.

[66] FIG. 5 shows a representative sensorgram for an Octet IL-18Rβ blocking assay.

[67] FIG. 6 with partial views FIG. 6A, FIG. 6B, and FIG. 6C shows rank-ordered binding responses of IL-18:IL-18Rα complex to antibody-blocked IL-18Rβ.

[68] FIG. 7 with partial views FIG. 7A, FIG. 7B, and FIG. 7C shows a combined binary dendrogram for candidate α-human IL-18Rβ blocking antibodies included in a LSA epitope binning assay.

[69] FIG. 8 shows a community node plot highlighting three main epitope bins for candidate α-huIL-18Rβ blocking antibodies.

[70] FIG. 9A-FIG. 9D show multi-pH sensorgrams for two α-human IL-18Rβ antibodies binding to human IL-18Rβ. FIG. 9A shows sensorgrams for P20 and P8 at a pH of 7.4; FIG. 9B shows sensorgrams for P20 and P8 at a pH of 5.0; FIG. 9C shows sensorgrams for P20 and P8 at a pH of 5.5; and FIG. 9D shows sensorgrams for P20 and P8 at a pH of 6.0.

[71] FIG. 10A shows a bar plot depicting the percent monomericity of antibody P20 at varying storage conditions using size exclusion chromatography.

[72] FIG. 10B shows a bar plot depicting the percent monomericity of antibody P21 at varying storage conditions using size exclusion chromatography.

[73] FIG. 10C shows a bar plot depicting the percent monomericity of antibody P8 at varying storage conditions using size exclusion chromatography.

[74] FIG. 11 depicts the chemical stability of three α-huIL-18Rβ antibodies as a function of time and temperature.

[75] FIG. 12 with partial views FIG. 12A and FIG. 12B shows a heat map for the light chain of antibody P20 assessing whether position D50 in the LCDR2 can be engineered to a different amino acid without losing activity, based on a deep mutational scan.

[76] FIG. 13 shows a bar plot depicting the percent monomericity of antibodies P20-V1 and P21-V1 at varying storage conditions using size exclusion chromatography.

[77] FIG. 14A shows the crystal structure of the IL-18Rβ+P20 fragment antibody binding (Fab) complex. Left, representation of the IL-18Rβ (molecular surface) epitope (dark grey) with the P20 Fab (cartoon; heavy chain, light grey; light chain, dark grey) paratope (sticks). Right, representation of the IL-18Rβ (cartoon) epitope (sticks) with the P20 Fab (molecular surface; heavy chain, light grey; light chain, medium grey) paratope (dark grey). Disordered internal loops represented as dashes.

[78] FIG. 14B shows the crystal structure of the IL-18Rβ+P8 fragment antibody binding (Fab) complex. Left, representation of the IL-18Rβ (molecular surface) epitope (dark grey) with the P8 Fab (cartoon; heavy chain, light grey; light chain, dark grey) paratope (sticks). Right, representation of the IL-18Rβ (cartoon) epitope (sticks) with the P8 Fab (molecular surface; heavy chain, light grey; light chain, medium grey) paratope (dark grey). Disordered internal loops represented as dashes.

[79] FIG. 14C shows crystal structures of different IL-18Rβ+anti-IL-18Rβ fragment antibody binding (Fab) complexes, where the complexes are IL-18Rβ+P20 Fab complex (left), IL-18Rβ+P20 Fab complex (middle), or IL-18Rβ+burosumab Fab complex (right). In each image, the HCDR3 of each anti-IL-18Rβ Fab is shown as a transparent surface and the LCDR2 of each anti-IL-18Rβ Fab is shown as dots.

[80] FIG. 15 depicts the inhibition of interferon gamma (IFNg or IFNg) in KG-1 cells when treated with anti-human IL-18Rβ monoclonal antibody P20-V1 (average of 7 independent experiments).

[81] FIG. 16 depicts the inhibition of interferon gamma (IFNg or IFNg) in human whole blood (LPS+IL-12 stimulation, n=15 donors) when treated with anti-human IL-18Rβ monoclonal antibody P20-V1.

[82] FIG. 17 depicts the inhibition of interferon gamma (IFNg or IFNg) in human whole blood (IL-18+IL-12 stimulation, n=8 donors) when treated with anti-human IL-18Rβ monoclonal antibody P20-V1.

[83] FIG. 18 depicts the inhibition of interferon gamma (IFNg or IFNg) in cynomolgus monkey whole blood (IL-18+IL-12 stimulation, n=14 donors) when treated with anti-human IL-18Rβ monoclonal antibody P20-V1.

[84] FIG. 19 depicts the dose-dependent exposure of anti-human IL-18Rβ monoclonal antibody P20-V1 in the serum of cynomolgus monkeys following P20-V1 administration in vivo.

[85] FIG. 20 depicts the sustained inhibition of interferon gamma (IFNg or IFNg) in an ex vivo cynomolgus monkey (cyno) whole blood assay where whole blood taken from cyno was stimulated with human IL-18 and IL-12 to induce IFNg production following administration of anti-human IL-18Rβ monoclonal antibody P20-V1 at the indicated doses in vivo. The top panel shows IFNg concentration and the bottom panel shows IFNg inhibition for the indicated experimental conditions.

[86] FIG. 21 depicts the lack of inhibition of interferon gamma (IFNg or IFNg) in wild-type mice whole blood stimulated with recombinant murine IL-18 and IL-12 when treated with anti-human IL-18Rβ monoclonal antibody P20-V1. The top panel shows IFNg concentration and the bottom panel shows IFNg inhibition for the indicated experimental conditions.

[87] FIG. 22 depicts the inhibition of interferon gamma (IFNg or IFNg) in human IL-18Rβ knock-in mice whole blood stimulated with recombinant murine IL-18 and IL-12 when treated with anti-human IL-18Rβ monoclonal antibody P20-V1. The top panel shows IFNg concentration and the bottom panel shows IFNg inhibition for the indicated experimental conditions.

[88] FIG. 23 depicts the lack of inhibition of interferon gamma (IFNg or IFNg) in wild-type mice splenocytes stimulated with recombinant murine IL-12 and LPS when treated with anti-human IL-18Rβ monoclonal antibody P20-V1. The top panel shows IFNg concentration and the bottom panel shows IFNg inhibition for the indicated experimental conditions.

[89] FIG. 24 depicts the interferon gamma (IFNg or IFNg)concentration (top panel) and inhibition of IFNg (bottom panel) in human IL-18Rβ knock-in mice splenocytes that were unstimulated, or stimulated with recombinant murine IL-12 and LPS when treated with anti-human IL-18Rβ monoclonal antibody P20-V1 or isotype control.

[90] FIG. 25 depicts IFNg (IFNg) concentration (left panel) and the inhibition of IFNg (right panel) in human IL-18Rβ knock-in mice whole blood that was unstimulated, or stimulated with IL-12 and IL-18 following in vivo administration of isotype control or anti-human IL-18Rβ monoclonal antibody P20-V1 at the indicated mg per kg (mpk) doses.

[91] FIG. 26 depicts the dose-dependent exposure of anti-human IL-18Rβ monoclonal antibody P20-V1 in the serum of human IL-18Rβ knock-in mice following P20-V1 administration in vivo.

[92] FIG. 27 depicts dose curve for ulcerative colitis (UC) lamina propria lymphocytes (LPLs) (n=7) pre-treated with P20-V1 or recombinant human IL-18 binding protein (IL-18BP) at various concentrations for 1 hour and stimulated with rhIL-12 (5 ng / ml) and rhIL-18 (6 ng / ml) for 24 hours. The top panel shows the IFNg (IFNg) concentration and the bottom panel shows percent inhibition of IFNg for the indicated experimental conditions.

[93] FIG. 28 depicts dose curve for Crohn’s disease (CD) lamina propria lymphocytes (LPLs) (n=8) pre-treated with P20-V1 or recombinant human IL-18 binding protein (IL-18BP) at various concentrations for 1 hour and stimulated with rhIL-12 (5 ng / ml) and rhIL-18 (6 ng / ml) for 24 hours. The top panel shows the IFNg (IFNg) concentration and the bottom panel shows percent inhibition of IFNg for the indicated experimental conditions.

[94] FIG. 29 depicts dose curves for healthy, i.e., non-inflammatory bowel disease (IBD) lamina propria lymphocytes (LPLs) (n=6) pre-treated with P20-V1 or recombinant human IL-18 binding protein (IL-18BP) at various concentrations for 1 hour and stimulated with rhIL-12 (5 ng / ml) and rhIL-18 (6 ng / ml) for 24 hours. The top panel shows the IFNg (IFNg) concentration and the right panel shows percent inhibition of IFNg for the indicated experimental conditions.

[95] FIGs. 30A-30C depict mRNA gene expression of IFNg (IFNG) (FIG. 30A), CXCL9 (FIG. 30B), and CXCL10 (FIG. 30C), respectively, of 3 donors of ulcerative colitis (UC) lamina propria lymphocytes (LPLs) pre-treated with P20-V1 at indicated concentrations for 1 hour and stimulated with rhIL-12 (5 ng / ml) and rhIL-18 (6 ng / ml) for 24 hours. Data was normalized to the GAPDH, ACTB, HPRT, RPLP0 and 18S house-keeping controls.

[96] FIG. 31 depicts body weight in a healthy control mouse model (PBS), or in an IL-12 / IL-18-induced colitis mice model following injection with a control isotype antibody (Isotype) or the indicated mg / kg (mpk) dose of anti-human IL-18Rβ monoclonal antibody P20-V1. Change in body weight over 4 days is shown in the left panel, and net change in body weight as quantified by area under the curve (AUC) is shown in the right panel.

[97] FIG. 32 depicts total (left) and damage (right) histology scores in the colon of healthy control mice (PBS), and in IL-12 / IL-18-induced colitis mice (IL-12 / IL-18) following injection with a control isotype antibody (Ig) or with the indicated dose of anti-human IL-18Rβ monoclonal antibody P20-V1.

[98] FIG. 33 depicts total (left) and damage (right) histology scores in the ileum of healthy control mice (PBS), and in IL-12 / IL-18-induced colitis mice (IL-12 / IL-18) following injection with a control isotype antibody (Ig) or with the indicated dose of anti-human IL-18Rβ monoclonal antibody P20-V1.

[99] FIG. 34 depicts levels of anti-human IL-18Rβ monoclonal antibody P20-V1 in the serum (left panel), colon (middle panel), or ileum (right panel) in an IL-12 / IL-18-induced colitis mouse model 120 hours post-administration of the indicated dose of P20-V1.

[100] FIG. 35 depicts IFNg (IFNg) concentration (left panel) and the inhibition of IFNg (right panel) in serum from a healthy control mouse model (PBS), or from an IL-12 / IL-18-induced colitis mouse model (IL-12 / -18) following in vivo administration of isotype control (Isotype) or anti-human IL-18Rβ monoclonal antibody P20-V1 at the indicated mg per kg (mpk) doses.

[101] FIG. 36 depicts IFNg (IFNg) concentration (left panel) and the inhibition of IFNg (right panel) in colons from a healthy control mouse model (PBS), or from an IL-12 / IL-18-induced colitis mouse model (IL-12 / -18) following in vivo administration of isotype control (Isotype) or anti-human IL-18Rβ monoclonal antibody P20-V1 at the indicated mg per kg (mpk) doses.

[102] FIG. 37 depicts IFNg (IFNg) concentration (left panel) and the inhibition of IFNg (right panel) in ileums from a healthy control mouse model (PBS), or from an IL-12 / IL-18-induced colitis mouse model (IL-12 / -18) following in vivo administration of isotype control (Isotype) or anti-human IL-18Rβ monoclonal antibody P20-V1 at the indicated mg per kg (mpk) doses.Detailed Description

[103] The present disclosure provides anti-IL-18Rβ antibodies and antigen-binding fragments thereof, as well as multi-specific antibodies and conjugates comprising the same, and nucleic acids and vectors encoding the same. Also provided herein are methods of producing the anti-IL-18Rβ antibodies and antigen-binding fragments thereof, the multi-specific antibodies, and conjugates, and compositions, e.g., pharmaceutical compositions, comprising any of the foregoing. Also provided are methods of using any of the anti-IL-18Rβ antibodies and antigen-binding fragments thereof, multi-specific antibodies, conjugates, or compositions described herein, such as in the treatment of a disease or disorder, diagnosis, assessing IL-18Rβ expression or activity, or in monitoring the treatment of a disease or disorder.

[104] IL-18 is a pro-inflammatory cytokine that is associated with a variety of diseases, including immune-mediated diseases, autoimmune diseases, inflammatory diseases, cancers, and infectious diseases.

[105] For instance, IL-18 has been implicated in having a pathogenic role in diseases and disorders including inflammatory bowel disease, e.g., Crohn’s disease and ulcerative colitis. The binding of IL-18Rβ to the IL-18 / IL-18Rα complex results in formation of an IL-18 receptor-ligand complex and activation of the TIR domain of the IL-18 receptor, which leads to signal propagation, including the production of interferon gamma (IFN-γ). This complex signals through activation of the Toll / IL-1 (TIR) domain, which is responsible for propagation of downstream signaling. Such activation of the TIR domain of the IL-18 receptor is known to promote the initiation and progression of diseases, including immune-mediated diseases, autoimmune diseases, inflammatory diseases, cancers, and infectious diseases. Blocking the binding of the IL-18Rβ subunit to the IL-18 / IL-18Rα complex can inhibit the downstream deleterious effects that occur through the IL-18 signaling pathway in such diseases and disorders, such as with regards to detrimental inflammatory responses. The anti-IL-18Rβ antibodies and antigen-binding fragments thereof provided herein advantageously block the binding of IL-18Rβ to the IL-18 / IL-18Rα complex to inhibit IL-18 signaling, while exhibiting additional structural and / or functional features that give rise to additional advantageous effects. These additional advantageous effects include, in some embodiments, high affinity binding to human and cynomolgus monkey IL-18Rβ; potency in inhibition of IFNg production; pH-independent binding; low polyreactivity to extracellular matrix proteins; stability; a low immunogenicity risk; and / or being a human antibody, or any combination thereof. In some embodiments, provided herein are anti-IL-18Rβ antibodies and antigen-binding fragments thereof that block the binding of IL-18Rβ to the IL-18 / IL-18Rα complex to inhibit IL-18 signaling, exhibit high affinity binding to human and cynomolgus monkey IL-18Rβ; exhibit potency in inhibition of IFNg production; exhibit pH-independent binding; exhibit low polyreactivity to extracellular matrix proteins; exhibit stability; exhibit a low immunogenicity risk; and are human.

[106] Among the provided anti-IL-18Rβ antibodies and antigen-binding fragments thereof are those that exhibit high affinity binding to both human and cynomolgus monkey IL-18Rβ. This is advantageous, for instance, because such antibodies can be used in preclinical studies (e.g., toxicology studies) in cynomolgus monkey; this obviates the need to use a different, surrogate antibody for such studies.

[107] In addition, in some embodiments, the provided anti-IL-18Rβ antibodies and antigen-binding fragments thereof exhibit potency in inhibition of IFNg production, including sustained inhibition over an extended period of time. This is advantageous because by blocking IL-18-induced IFNg production that is characteristic of many diseases and disorders mediated, at least in part, by IL-18 pathway signaling, such diseases and disorders can be treated.

[108] In addition, in some embodiments, the provided anti-IL-18Rβ antibodies and antigen-binding fragments thereof exhibit pH-independent binding. This is advantageous because the anti-IL-18Rβ antibody or antigen-binding fragment thereof can bind to IL-18Rβ at physiological pH, while also binding to IL-18Rβ in more acidic environments, such as the gastrointestinal tract, e.g., for treatment of inflammatory bowel disease, or in tumor microenvironments, e.g., for treatment of cancers, among other acidic environments.

[109] In addition, in some embodiments, the provided anti-IL-18Rβ antibodies and antigen-binding fragments thereof exhibit low polyreactivity to extracellular matrix (ECM) proteins. This is advantageous because low polyreactivity with ECM proteins can reduce off-target effects caused by the antibody binding to ECM proteins, and can reduce or avoid the negative effects that polyreactivity can have on pharmacokinetics and bioavailability of the antibody.

[110] In addition, in some embodiments, the provided anti-IL-18Rβ antibodies and antigen-binding fragments thereof exhibit stability as evidenced by, e.g., low surface hydrophobicity and low self-interaction propensity (thereby reducing the risk of self-aggregation), low monomericity, low charge heterogeneity, and / or low (or absent) chemical liability risk. Among the provided anti-IL-18Rβ antibodies and antigen-binding fragments thereof include those in which a chemical liability risk is reduced or eliminated by introducing an amino acid mutation, (e.g., a mutation of D50 in the light chain variable region, such as, e.g., a D50E or D50G mutation in the light chain variable region) to substitute the amino acid identified as posing a chemical liability risk. In some embodiments, the provided anti-IL-18Rβ antibodies and antigen-binding fragments thereof include those in which, advantageously, a chemical instability risk is eliminated, e.g., by a D50 mutation (e.g., a D50E or D50G mutation) in the light chain variable region, without negatively impacting its: (i) binding to human and cynomolgus monkey IL-18Rβ, including pH-independent binding, (ii) potency in inhibiting IFNg production; and / or (iii) low immunogenicity risk, as compared to the parental antibody that has the chemical instability risk.

[111] In addition, in some embodiments, the provided anti-IL-18Rβ antibodies and antigen-binding fragments thereof exhibit a low immunogenicity risk, as determined, e.g., by a low response rate observed in donors. In some embodiments, the antibody or antigen-binding fragment thereof is human, thereby contributing to a low immunogenicity risk.

[112] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen binding fragments include one or more mutations (e.g., framework revertant mutations) disclosed herein. In some embodiments, the antibodies or antigen binding fragments include Q6E in the heavy chain variable region. In some embodiments, the antibodies or antigen binding fragments do not include F46L in the light chain variable region.

[113] All publications, including patent documents, scientific articles and databases, referred to in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication were individually incorporated by reference. If a definition set forth herein is contrary to or otherwise inconsistent with a definition set forth in the patents, applications, published applications and other publications that are herein incorporated by reference, the definition set forth herein prevails over the definition that is incorporated herein by reference.

[114] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. I. Anti-IL-18RβAntibodies AND antigen-binding fragments THEREOF

[115] Provided herein are anti-IL-18Rβ antibodies and antigen-binding fragments thereof. Among the provided anti-IL-18Rβ antibodies and antigen-binding fragments thereof are those that exhibit one or more (e.g., at least two, three, four, five, or all) of the following advantageous technical effects: high affinity binding to human and cynomolgus monkey IL-18Rβ; potency, for instance, in inhibition of IFNg production; pH-independent binding; low polyreactivity; blocking of IL-18Rβ interaction with the IL-18 / IL-18Rα complex; and a low immunogenicity risk.

[116] Among the provided embodiments of anti-IL-18Rβ antibodies and antigen-binding fragments thereof are variants of the anti-IL-18Rβ antibodies and antigen-binding fragments thereof disclosed herein, such as variants having at least 85%, 90%, or 95% sequence identity to a reference antibody. In some embodiments, the variants are variants of antibody P20 or antibody P8. In some embodiments, the variants are variants of antibody P20 and include P20-V1, P20-V2, and P20-V3. In some embodiments, the variants are variants of antibody P8 and include P8-V1.

[117] Among the provided embodiments of anti-IL-18Rβ antibodies and antigen-binding fragments thereof are multi-specific antibodies, such as bispecific antibodies, that comprise a first antigen-binding domain comprising any of the anti-IL-18Rβ antibodies and antigen-binding fragments thereof disclosed herein, and a second antigen-binding domain that binds to a second antigen.

[118] Also provided herein are conjugates comprising an anti-IL-18Rβ antibody or antigen-binding fragment thereof disclosed herein and a heterologous molecule or moiety.A. Exemplary Antibodies and Antigen-Binding Fragments Thereof

[119] Provided herein are anti-IL-18Rβ antibodies and antigen-binding fragments thereof, including those having the sequences as described herein, such as those as described in Tables provided in the Examples (e.g., Tables E12A and E16A). In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a VH region that comprises a CDR-H1, a CDR-H2, and a CDR-H3 as described, and comprises a VL region that comprises a CDR-L1, a CDR-L2, and a CDR-L3 as described. In the present disclosure, it is understood that reference to a sequence (such as, but not limited to, sequences for a VH region or heavy chain) by a SEQ ID NO includes the corresponding amino acid sequence or the corresponding amino acid sequence comprising a post-translational modification. Post-translational modifications can include, e.g., glycosylation, phosphorylation, citrullination, isomerization, ubiquitination, acetylation, hydroxylation, methylation, AMPylation, prenylation, deamidation, eliminylation, carbamylation and carbamoylation.

[120] In some embodiments, the post-translational modification is the modification of an amino acid side chain, such as conversion of an N-terminal amino acid (e.g., glutamate or glutamine) to pyroglutamate. In some such embodiments, this modification occurs at the N-terminus of the heavy chain. In a particular example, an antibody or antigen binding fragment thereof that comprises the amino acid sequence SEQ ID NO: 32 may include a post-translational modification to SEQ ID NO: 32, such that the N-terminal glutamine (Q) residue of SEQ ID NO: 32 is post-translationally modified to pyroglutamate as set forth in SEQ ID NO:159, wherein X is a pyroglutamate. In another particular example, an antibody or antigen binding fragment thereof that comprises the amino acid sequence SEQ ID NO: 34 may include a post-translational modification to SEQ ID NO: 34, such that the N-terminal glutamine (Q) residue of SEQ ID NO: 34 is post-translationally modified to pyroglutamate as set forth in SEQ ID NO:160, wherein X is a pyroglutamate. In another particular example, an antibody or antigen binding fragment thereof that comprises the amino acid sequence SEQ ID NO: 73 may include a post-translational modification to SEQ ID NO: 73, such that the N-terminal glutamine (Q) residue of SEQ ID NO: 73 is post-translationally modified to pyroglutamate as set forth in SEQ ID NO:162, wherein X is a pyroglutamate. In another particular example, an antibody or antigen binding fragment thereof that comprises the amino acid sequence SEQ ID NO: 75 may include a post-translational modification to SEQ ID NO: 75, such that the N-terminal glutamine (Q) residue of SEQ ID NO: 75 is post-translationally modified to pyroglutamate as set forth in SEQ ID NO:163, wherein X is a pyroglutamate. In some embodiments, in a composition of an antibody or antigen-binding fragment thereof as disclosed herein, such a post-translational modification to pyroglutamate (e.g., at the N-terminus of the heavy chain, e.g., at the N-terminus of SEQ ID NO: 34) is a dominant post-translational modification; in some such embodiments, the antibody or antigen binding fragment thereof in which an N-terminal pyroglutamate is present represents greater than 50%, greater than 60%, greater than 70%, greater than 80%, greater than 90%, or greater than 95% (w / w) of the antibody or antigen binding fragment thereof in the composition.

[121] In some embodiments, the post-translational modification is the cleavage of one or more, particularly one or two, amino acids from the C-terminus of the heavy chain. For instance, an antibody produced by expression of a specific nucleic acid molecule encoding a full-length heavy chain (e.g., by expression in a host cell) may include the full-length heavy chain, or it may include a cleaved variant of the full-length heavy chain. This may be the case where the final two C-terminal amino acids of the heavy chain are glycine and lysine, respectively. Therefore, the C-terminal lysine, or the C-terminal glycine and lysine, of the Fc region may or may not be present. Thus, a heavy chain constant domain or an anti-IL-18Rβ antibody may include a heavy chain constant domain with both a C-terminal glycine and lysine, without the C-terminal lysine, or without both the C-terminal glycine and lysine. In some embodiments, in a composition of an antibody or antigen-binding fragment thereof as disclosed herein, glycine cleavage is not a dominant post-translational modification; in some such embodiments, the antibody or antigen binding fragment thereof in which the C-terminal lysine is cleaved from the heavy chain constant domain represents less than 10%, less than 5%, or less than 4% (w / w) of the antibody or antigen binding fragment thereof in the composition.

[122] Provided herein, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 34; and the VL region comprises a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 35.

[123] Also provided, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 34; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 35.

[124] Also provided, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 8, 11, 13, 15, and 18, a heavy chain complementarity determining region 2 (CDR-H2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 9, 12, 14, 16, and 19, and a heavy chain complementarity determining region 3 (CDR-H3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 17, and 20; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 25, and 28, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 36, 37, and 38, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24 or 27.

[125] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 36, and 24, respectively; wherein the numbering is according to Kabat numbering.

[126] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 11, 12, and 10, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 36, and 24, respectively; wherein the numbering is according to Chothia numbering.

[127] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 13, 14, and 10, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 36, and 24, respectively; wherein the numbering is according to AbM numbering.

[128] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 15, 16, and 17, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 25, 37, and 27, respectively; wherein the numbering is according to Contact numbering.

[129] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 18, 19, and 20, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 28, 38, and 24, respectively; wherein the numbering is according to IMGT numbering.

[130] In some embodiments, provided herein is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 8, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 9, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 10; and the VL region comprises a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24. In some embodiments, the VL region further comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 22, and a light chain complementarity determining region 2 (CDR-L2) comprising the amino acid sequence of SEQ ID NO: 36.

[131] In some embodiments, provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 8, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 9, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 10; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 22, a light chain complementarity determining region 2 (CDR-L2) comprising the amino acid sequence of SEQ ID NO: 36, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24.

[132] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 34.

[133] In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region does not comprise D at position 50. In some such embodiments, the VL region comprises E or G at position 50. In some such embodiments, the VL region comprises E at position 50. In some embodiments, the VL region comprises E at position 50 and G at position 51. In some embodiments, the VL region comprises F at position 46. In some embodiments, the VL region comprises F at position 46 and D at position 50. In some embodiments, the VL region does not comprise L at position 46.

[134] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 35.

[135] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises the amino acid sequence of SEQ ID NO: 34, wherein the N-terminal glutamine (Q) residue of SEQ ID NO: 34 is post-translationally modified to pyroglutamine. In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 35.

[136] In some embodiments, the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 35.

[137] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 35.

[138] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody comprising a constant domain, such as any constant domain as described herein. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody, and the VH region is comprised within a heavy chain and the VL region is comprised within a light chain.

[139] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 32.

[140] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 33.

[141] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 33.

[142] In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 33. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 33.

[143] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32, and at least one post-translational modification of the amino acid sequence of SEQ ID NO:32 is present. In some such embodiments, the at least one post-translational modification includes a post-translational modification of the N-terminal glutamine (Q) residue of SEQ ID NO: 32 to a pyroglutamine. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 33.

[144] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 33. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; and a light chain comprising the amino acid sequence of SEQ ID NO: 33.

[145] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32, and a light chain comprising the amino acid sequence of SEQ ID NO: 33.

[146] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antigen-binding fragment thereof, such as any of those as described herein.

[147] Also provided herein, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a VH region that comprises, consists essentially of, or consists of (a) an amino acid sequence having at least, or at least about, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 34 and (b) a VL region that comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 21 or SEQ ID NO: 35. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 90% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 95% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 96% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 97% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 98% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 99% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, VH region comprises E at position 6. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 90% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about,95% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 96% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 97% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 98% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about, 99% sequence identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the VL region does not comprise D at position 50. In some such embodiments, the VL region comprises G or E at position 50. In some embodiments, the VL region comprises E at position 50 and G at position 51. In some embodiments, the VL region comprises F at position 46. In some embodiments, the VL region comprises F at position 46 and D at position 50. In some embodiments, the VL region does not comprise L at position 46.

[148] Also provided herein, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 51; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 65.

[149] Also provided, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 52, 55, 57, 59, and 62, a heavy chain complementarity determining region 2 (CDR-H2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 53, 56, 58, 60, and 63, and a heavy chain complementarity determining region 3 (CDR-H3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 54, 61, and 64; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 66, 69, and 72, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 67, 70, and 29, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 68 or 71.

[150] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 52, 53, and 54, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; wherein the numbering is according to Kabat numbering.

[151] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 55, 56, and 54, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; wherein the numbering is according to Chothia numbering.

[152] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 57, 58, and 54, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; wherein the numbering is according to AbM numbering.

[153] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 59, 60, and 61, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 69, 70, and 71, respectively; wherein the numbering is according to Contact numbering.

[154] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 62, 63, and 64, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 72, 29, and 68, respectively; wherein the numbering is according to IMGT numbering.

[155] In some embodiments, provided herein is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 52, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 53, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 54; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 66, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 67, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 68.

[156] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 51. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 51.

[157] In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 65.

[158] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 65.

[159] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 51. In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 65.

[160] In some embodiments, the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 65. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 65.

[161] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 51; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 65.

[162] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody comprising a constant domain, such as any constant domain as described herein. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody, and the VH region is comprised within a heavy chain and the VL region is comprised within a light chain.

[163] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 49. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 49. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 49. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 49. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 49. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 49. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 49. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 49.

[164] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 50.

[165] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 49; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 50.

[166] In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 49; and the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 49; and the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 49; and the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 49; and the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 49; and the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 49; and the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 50. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 49; and the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 50.

[167] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 49. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 49; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 50.

[168] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 50. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 49; and a light chain comprising the amino acid sequence of SEQ ID NO: 50.

[169] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 49, and a light chain comprising the amino acid sequence of SEQ ID NO: 50.

[170] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antigen-binding fragment thereof, such as any of those as described herein.

[171] Also provided herein, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 7; and the VL region comprises a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 21.

[172] Also provided, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 8, 11, 13, 15, and 18, a heavy chain complementarity determining region 2 (CDR-H2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 9, 12, 14, 16, and 19, and a heavy chain complementarity determining region 3 (CDR-H3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 17, and 20; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 25, and 28, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 23, 26, and 29, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24 or 27.

[173] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 23, and 24, respectively; wherein the numbering is according to Kabat numbering.

[174] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 11, 12, and 10, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 23, and 24, respectively; wherein the numbering is according to Chothia numbering.

[175] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 13, 14, and 10, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 23, and 24, respectively; wherein the numbering is according to AbM numbering.

[176] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 15, 16, and 17, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 25, 26, and 27, respectively; wherein the numbering is according to Contact numbering.

[177] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 18, 19, and 20, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 28, 29, and 24, respectively; wherein the numbering is according to IMGT numbering.

[178] In some embodiments, provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 8, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 9, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 10; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 22, a light chain complementarity determining region 2 (CDR-L2) comprising the amino acid sequence of SEQ ID NO: 23, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24.

[179] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 7.

[180] In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 21.

[181] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 21.

[182] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 7. In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 21.

[183] In some embodiments, the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 21. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 21.

[184] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 7; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 21.

[185] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody comprising a constant domain, such as any constant domain as described herein. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody, and the VH region is comprised within a heavy chain and the VL region is comprised within a light chain.

[186] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 5. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 5.

[187] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 6.

[188] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 5; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 6.

[189] In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 5; and the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 5; and the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 5; and the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 5; and the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 5; and the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 5; and the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 6. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 5; and the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 6.

[190] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 5. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 5; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 6.

[191] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 5; and a light chain comprising the amino acid sequence of SEQ ID NO: 6.

[192] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 5, and a light chain comprising the amino acid sequence of SEQ ID NO: 6.

[193] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antigen-binding fragment thereof, such as any of those as described herein.

[194] Also provided herein, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 34; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 40 or 45.

[195] Also provided, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 8, 11, 13, 15, and 18, a heavy chain complementarity determining region 2 (CDR-H2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 9, 12, 14, 16, and 19, and a heavy chain complementarity determining region 3 (CDR-H3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 17, and 20; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 25, and 28, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 41-43 and 46-48, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24 or 27.

[196] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively; and the VL region comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 22, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 41 or 46, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 24; wherein the numbering is according to Kabat numbering.

[197] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 11, 12, and 10, respectively; and the VL region comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 22, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 41 or 46, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 24; wherein the numbering is according to Chothia numbering.

[198] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 13, 14, and 10, respectively; and the VL region comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 22, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 41 or 46, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 24; wherein the numbering is according to AbM numbering.

[199] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 15, 16, and 17, respectively; and the VL region comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 25, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 42 or 47, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 27; wherein the numbering is according to Contact numbering.

[200] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 18, 19, and 20, respectively; and the VL region comprises a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 28, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 43 or 48, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 24; wherein the numbering is according to IMGT numbering.

[201] In some embodiments, provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 41, and 24, respectively.

[202] In some embodiments, provided herein is an anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 46, and 24, respectively.

[203] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 34.

[204] In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 45. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45.

[205] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 45.

[206] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45.

[207] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 34. In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 40 or 45.

[208] In some embodiments, the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 40. In some embodiments, the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 45. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 40 or 45.

[209] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 40 or 45. In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 40. In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 34; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 45.

[210] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody comprising a constant domain, such as any constant domain as described herein. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody, and the VH region is comprised within a heavy chain and the VL region is comprised within a light chain.

[211] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 32. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 32.

[212] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 39. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44.

[213] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 39. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 44.

[214] In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; and the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44.

[215] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 39 or 44.

[216] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 39. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 44. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; and a light chain comprising the amino acid sequence of SEQ ID NO: 39 or 44.

[217] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32, and a light chain comprising the amino acid sequence of SEQ ID NO: 39 or 44. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32, and a light chain comprising the amino acid sequence of SEQ ID NO: 39. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32, and a light chain comprising the amino acid sequence of SEQ ID NO: 44.

[218] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antigen-binding fragment thereof, such as any of those as described herein.

[219] Also provided herein, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 75; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 76.

[220] Also provided, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 52, 55, 57, 59, and 62, a heavy chain complementarity determining region 2 (CDR-H2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 53, 56, 58, 60, and 63, and a heavy chain complementarity determining region 3 (CDR-H3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 54, 61, and 64; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 66, 69, and 72, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 67, 70, and 29, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 68 or 71.

[221] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 52, 53, and 54, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; wherein the numbering is according to Kabat numbering.

[222] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 55, 56, and 54, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; wherein the numbering is according to Chothia numbering.

[223] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 57, 58, and 54, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 66, 67, and 68, respectively; wherein the numbering is according to AbM numbering.

[224] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 59, 60, and 61, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 69, 70, and 71, respectively; wherein the numbering is according to Contact numbering.

[225] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 62, 63, and 64, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 72, 29, and 68, respectively; wherein the numbering is according to IMGT numbering.

[226] In some embodiments, provided herein is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 52, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 53, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 54; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 66, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 67, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 68.

[227] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 75.

[228] In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 76.

[229] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 76.

[230] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 75. In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 76.

[231] In some embodiments, the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 76. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 76.

[232] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 75; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 76.

[233] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody comprising a constant domain, such as any constant domain as described herein. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody, and the VH region is comprised within a heavy chain and the VL region is comprised within a light chain.

[234] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 73. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 73. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 73. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 73. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 73. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 73. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 73. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 73.

[235] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 74.

[236] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 73; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 74.

[237] In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 73; and the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 73; and the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 73; and the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 73; and the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 73; and the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 73; and the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 73; and the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 74.

[238] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 73. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 73; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 74.

[239] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 74. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 73; and a light chain comprising the amino acid sequence of SEQ ID NO: 74.

[240] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 73, and a light chain comprising the amino acid sequence of SEQ ID NO: 74.

[241] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antigen-binding fragment thereof, such as any of those as described herein.

[242] Also provided herein, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 79; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 93.

[243] Also provided, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 80, 83, 85, 87, and 90, a heavy chain complementarity determining region 2 (CDR-H2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 81, 84, 86, 88, and 91, and a heavy chain complementarity determining region 3 (CDR-H3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 82, 89, and 92; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 25, and 28, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 94, 96, and 29, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 95 or 97.

[244] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 80, 81, and 82, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 94, and 95, respectively; wherein the numbering is according to Kabat numbering.

[245] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 83, 84, and 82, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 94, and 95, respectively; wherein the numbering is according to Chothia numbering.

[246] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 85, 86, and 82, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 94, and 95, respectively; wherein the numbering is according to AbM numbering.

[247] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 87, 88, and 89, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 25, 96, and 97, respectively; wherein the numbering is according to Contact numbering.

[248] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 90, 91, and 92, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 28, 29, and 95, respectively; wherein the numbering is according to IMGT numbering.

[249] In some embodiments, provided herein is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 80, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 81, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 82; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 22, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 94, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 95.

[250] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 79. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 79. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 79. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 79. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 79. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 79. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 79. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 79.

[251] In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 93.

[252] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 93.

[253] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 79. In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 93.

[254] In some embodiments, the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 93. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 93.

[255] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 79; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 93.

[256] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody comprising a constant domain, such as any constant domain as described herein. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody, and the VH region is comprised within a heavy chain and the VL region is comprised within a light chain.

[257] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 77. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 77.

[258] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 78.

[259] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 77; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 78.

[260] In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 77; and the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 77; and the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 77; and the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 77; and the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 77; and the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 77; and the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 78. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 77; and the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 78.

[261] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 77. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 77; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 78.

[262] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 78. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 77; and a light chain comprising the amino acid sequence of SEQ ID NO: 78.

[263] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 77, and a light chain comprising the amino acid sequence of SEQ ID NO: 78.

[264] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antigen-binding fragment thereof, such as any of those as described herein.

[265] Also provided herein, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 100; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 101.

[266] Also provided, in some embodiments, is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 80, 83, 85, 87, and 90, a heavy chain complementarity determining region 2 (CDR-H2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 81, 84, 86, 88, and 91, and a heavy chain complementarity determining region 3 (CDR-H3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 82, 89, and 92; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 25, and 28, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 102, 103, and 38, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 95 or 97.

[267] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 80, 81, and 82, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 102, and 95, respectively; wherein the numbering is according to Kabat numbering.

[268] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 83, 84, and 82, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 102, and 95, respectively; wherein the numbering is according to Chothia numbering.

[269] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 85, 86, and 82, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 102, and 95, respectively; wherein the numbering is according to AbM numbering.

[270] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 87, 88, and 89, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 25, 103, and 97, respectively; wherein the numbering is according to Contact numbering.

[271] In some embodiments, the VH region comprises a CDR-H1, a CDR-H2, and a CDR-H3 comprising the amino acid sequences of SEQ ID NOs: 90, 91, and 92, respectively; and the VL region comprises a CDR-L1, a CDR-L2, and a CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 28, 38, and 95, respectively; wherein the numbering is according to IMGT numbering.

[272] In some embodiments, provided herein is an anti-IL-18Rβ antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 80, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 81, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 82; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 22, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 102, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 95.

[273] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 100.

[274] In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 101.

[275] In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 101.

[276] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 100. In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 101.

[277] In some embodiments, the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 101. In some embodiments, the VH region comprises, consists essentially of, or consists of an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 101.

[278] In some embodiments, the VH region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 100; and the VL region comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 101.

[279] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody comprising a constant domain, such as any constant domain as described herein. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody, and the VH region is comprised within a heavy chain and the VL region is comprised within a light chain.

[280] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 98. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 98.

[281] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 99.

[282] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 98; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 99.

[283] In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 98; and the light chain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 98; and the light chain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 98; and the light chain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 98; and the light chain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 98; and the light chain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 98; and the light chain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 99. In some embodiments, the heavy chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 98; and the light chain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 99.

[284] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 98. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 98; and a light chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 99.

[285] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 99. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising an amino acid sequence having at least, or at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 98; and a light chain comprising the amino acid sequence of SEQ ID NO: 99.

[286] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 98, and a light chain comprising the amino acid sequence of SEQ ID NO: 99.

[287] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antigen-binding fragment thereof, such as any of those as described herein.

[288] In some of any of the embodiments provided herein, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a constant domain. In some of any of the embodiments provided herein, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody comprising a constant domain.

[289] In certain embodiments, antibody variable domains as described are fused to immunoglobulin constant domain sequences. In certain embodiments, the fusion is with an Ig heavy chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. In some of any of the embodiments herein, the antibody further comprises a heavy chain constant domain and / or a light chain constant domain. In some embodiments, the heavy chain and / or light constant domain is human.

[290] In general, the “constant region” or “constant domain” contains a sequence of amino acids that is comparatively more conserved among antibodies than the variable region domain. The constant regions of immunoglobulins show less sequence diversity than the variable regions, and are responsible for binding a number of natural proteins to elicit important biochemical events. Each light chain has a single light chain constant region (CL) domain, which is either of the kappa or lambda type. Each heavy chain contains one or more heavy chain constant region (CH) domains that can be assigned to different classes or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM, having heavy chains designated , , ,  and , respectively. Full-length IgA, IgD and IgG isotypes contain CH1, CH2, CH3and a hinge region, while IgE and IgM contain CH1, CH2, CH3 and CH4. The  and  classes are further divided into subclasses on the basis of relatively minor differences in the CH sequence and function, e.g., humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2. IgG1 antibodies can exist in multiple polymorphic variants termed allotypes (reviewed in Jefferis and Lefranc 2009. mAbs Vol 1 Issue 4 1-7) any of which are suitable. In humans there are five different classes of antibodies including IgA (which includes subclasses IgA1 and IgA2), IgD, IgE, IgG (which includes subclasses IgG1, IgG2, IgG3, and IgG4), and IgM. The distinguishing features between these antibody classes are their constant, Fc regions, although subtler differences may exist in the V region. An antibody constant region can include an Fc portion. Although the boundaries of the Fc region of an immunoglobulin heavy chain might vary, the human IgG heavy-chain Fc region usually includes the region containing the CH2 and CH3 domains and the hinge region, such as an amino acid residue at position Cys226, or from Pro230, to the carboxyl-terminus thereof.

[291] In some embodiments, the constant domain is a constant domain selected from the group consisting of an IgA1 constant domain, an IgA2 constant domain, an IgD constant domain, an IgE constant domain, a IgG1 constant domain, an IgG2 constant domain, an IgG3 constant domain, an IgG4 constant domain, and an IgM constant domain. In some embodiments, the constant domain is a human constant domain, e.g., a human constant domain selected from the group consisting of an IgA1 constant domain, an IgA2 constant domain, an IgD constant domain, an IgE constant domain, an IgG1 constant domain, an IgG2 constant domain, an IgG3 constant domain, an IgG4 constant domain, and an IgM constant domain. In some embodiments, the constant domain is an IgG1 constant domain. In some embodiments, the constant domain is a human IgG1 constant domain.

[292] In certain embodiments, a provided antibody contains an Ig heavy chain constant domain comprising at least part of the hinge, CH2, and CH3 regions. Certain embodiments have the first heavy-chain constant region (CH1) containing the site necessary for light chain bonding, present in at least one of the fusions. DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host cell. This provides for greater flexibility in adjusting the mutual proportions of the three polypeptide fragments in embodiments when unequal ratios of the three polypeptide chains used in the construction provide the optimum yield of the desired fusion antibody. It is, however, possible to insert the coding sequences for two or all three polypeptide chains into a single expression vector when the expression of at least two polypeptide chains in equal ratios results in high yields or when the ratios have no significant effect on the yield of the desired chain combination.

[293] In some embodiments, the antibody or antigen-binding fragment thereof, may contain at least a portion of an immunoglobulin constant region, such as one or more constant region domain. In some embodiments, the constant regions include a light chain constant region and / or a heavy chain constant region 1 (CH1). In some embodiments, the antibody includes at least a portion of a hinge region or a variant thereof. In some embodiments, the antibody includes a CH2 and / or CH3 domain, such as an Fc region. In some embodiments, the Fc region is an Fc region from an IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, or IgM. In some embodiments, the constant domain of the antibody comprises CH2 and CH3 domains from one or more of the different Ig classes.

[294] In some embodiments, the heavy chain constant sequence includes an IgG4 containing the S228P mutation, which has been shown to prevent recombination between a therapeutic antibody and an endogenous IgG4 by Fab-arm exchange (see e.g. Labrijin et al. (2009) Nat. Biotechnol., 27(8): 767-71.)

[295] In some embodiments, the constant domain of the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a heavy chain constant domain and a light chain constant domain. In some embodiments, the antibody comprises a heavy chain constant domain and a light chain constant domain.

[296] In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30. In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 30. In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 30. In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 30. In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 30. In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 30. In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 30. In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 30.

[297] In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31. In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 31. In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 31. In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 31. In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 96% sequence identity to the amino acid sequence of SEQ ID NO: 31. In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 31. In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 98% sequence identity to the amino acid sequence of SEQ ID NO: 31. In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 31.

[298] In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and the light chain constant domain comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31.

[299] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 30. In some embodiments, the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 31.

[300] In some embodiments, the heavy chain constant domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122.

[301] In some embodiments, the heavy chain constant domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122. In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122.

[302] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 104, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 104. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 106, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 106. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 108, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 108. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 110, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 112, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 114, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 116, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 118, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 118. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 120, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 122, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 122.

[303] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 104. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 106. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 108. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 110. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 112. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 114. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 116. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 118. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 120. In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 122.

[304] In some embodiments, the heavy chain constant domain is encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 105, 107, 109, 111, 113, 115, 117, 119, 121, and 123, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 105, 107, 109, 111, 113, 115, 117, 119, 121, and 123.

[305] In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 105, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 105. In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 107, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 107. In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 109, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 109. In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 111, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 111. In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 113, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 113. In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 115, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 115. In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 117, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 117. In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 119, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 119. In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 121, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 121. In some embodiments, the heavy chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 123, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 123.

[306] In some embodiments, the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 31 or 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31 or 124.

[307] In some embodiments, the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 31 or 124. In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31 or 124.

[308] In some embodiments, the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124. In some embodiments, the light chain constant domain comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[309] In some embodiments, the light chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 125, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 125.

[310] In some embodiments, the heavy chain constant domain is encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 105, 107, 109, 111, 113, 115, 117, 119, 121, and 123, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 105, 107, 109, 111, 113, 115, 117, 119, 121, and 123; and the light chain constant domain is encoded by the nucleic acid sequence of SEQ ID NO: 125, or a nucleic acid having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleic acid sequence of SEQ ID NO: 125.

[311] In some embodiments, the heavy chain constant domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 31 or 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31 or 124.

[312] In some embodiments, the heavy chain constant domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 31 or 124.

[313] In some embodiments, the heavy chain constant domain comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122; and the light chain constant domain comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31 or 124.

[314] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 30, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[315] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 104, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 104; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[316] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 106, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 106; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[317] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 108, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 108; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[318] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 110, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 110; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[319] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 112, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 112; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[320] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 114, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 114; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[321] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 116, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 116; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[322] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 118, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 118; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[323] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 120, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 120; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[324] In some embodiments, the heavy chain constant domain comprises the amino acid sequence of SEQ ID NO: 122, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 122; and the light chain constant domain comprises the amino acid sequence of SEQ ID NO: 124, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 124.

[325] Sequences of anti-IL-18Rβ antibodies and antigen-binding fragments thereof disclosed herein, in some embodiments, are provided in Table E12A and Table E16A in the Examples.

[326] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof are human antibodies, or antibodies or antigen-binding fragments thereof that are modified from or variants of human antibodies. The anti-IL-18Rβ antibodies or antigen-binding fragments thereof include isolated antibodies.

[327] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antigen-binding fragment. In some embodiments, the antigen-binding fragment is selected from the group consisting of fragment antigen binding (Fab) fragments, F(ab’)2 fragments, Fab’ fragments, Fv fragments, recombinant IgG (rIgG) fragments, heavy chain variable (VH) regions capable of specifically binding the antigen, single chain antibody fragments, including single chain variable fragments (scFv), and single domain antibodies (e.g., sdAb, sdFv, nanobody, VHH) fragments.

[328] In some embodiments, the anti-IL-18Rβ antibodies or antigen-binding fragments thereof include genetically engineered and / or otherwise modified forms of immunoglobulins, such as intrabodies, peptibodies, chimeric antibodies, fully human antibodies, humanized antibodies, and heteroconjugate antibodies, multi-specific antibodies, e.g., bispecific or trispecific antibodies, diabodies, triabodies, and tetrabodies, tandem di-scFv, tandem tri-scFv. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an intact or full-length antibody. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an intact or full-length antibody comprising a constant domain. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antibody or antigen-binding fragment thereof of any class or sub-class, including IgG and sub-classes thereof, IgM, IgE, IgA, and IgD.

[329] In general, antibodies and antigen-binding fragments thereof include complementarity determining regions (CDRs) and framework regions (FRs) in their variable regions. CDRs are known to refer to non-contiguous sequences of amino acids within antibody variable regions, which confer antigen specificity and / or binding affinity. In general, there are three CDRs in each heavy chain variable region (CDR-H1, CDR-H2, CDR-H3) and three CDRs in each light chain variable region (CDR-L1, CDR-L2, CDR-L3), which are separated by FRs that refer to the non-CDR portions of the variable regions of the heavy and light chains. In general, there are four FRs in each full-length heavy chain variable region (FR-H1, FR-H2, FR-H3, and FR-H4), and four FRs in each full-length light chain variable region (FR-L1, FR-L2, FR-L3, and FR-L4).

[330] The precise amino acid sequence boundaries of a given CDR or FR can be readily determined using any of a number of well-known schemes, including those described by Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (“Kabat” numbering scheme); Al-Lazikani et al., J Mol Biol, 1997; 273(4):927-48 (“Chothia” numbering scheme); MacCallum et al., J. Mol. Biol, 1996; 262:732-745.” (“Contact” numbering scheme); Lefranc MP et al., Dev Comp Immunol, 2003; 27(1):55-77 (“IMGT” numbering scheme); Honegger A and Plückthun A, J Mol Biol, 2001; 309(3):657-70, (“Aho” numbering scheme); Martin et al., PNAS, 1989; 86(23):9268-9272, (“AbM” numbering scheme); and Ye et al., Nucleic Acids Res. 2013; 41(Web Server issue):W34-40, (“IgBLAST numbering scheme). Details regarding various numbering schemes are also described in, for example, Jarasch et al., Proteins, 2017; 85(1):65-71; Martin et al., Bioinformatics tools for antibody engineering. In: Dübel, S. (editor) Handbook of Therapeutic Antibodies, Vol. 1. Wiley-VCH, Weinheim, Germany; Martin, A.C.R. (2010). Protein Sequence and Structure Analysis of Antibody Variable Domains. In: Kontermann, R., Dübel, S. (eds) Antibody Engineering. Springer Protocols Handbooks. Springer, Berlin, Heidelberg; and Martin, ACR, Antibody Information: How to identify the CDRs by looking at a sequence [online] bioinf.org.uk / abs / info.html, all of which are incorporated by reference in their entireties. Various prediction algorithm tools are available and known for numbering antibody residues and CDRs (e.g., AbYsis, Abnum, AbYmod, AbRSA, IgBLAST, IMGT, or ANARCI).

[331] The boundaries of a given CDR or FR may vary depending on the scheme used for identification. For example, the Kabat scheme is based on structural alignments, while the Chothia scheme is based on structural information. Numbering for both the Kabat and Chothia schemes is based upon the most common antibody region sequence lengths, in some cases with insertions. Insertions in the sequence relative to the standard numbering scheme are indicated using insertion letter codes. For example, residues that are inserted between residues L30 and L31 are indicated as L31A, L31B, etc. Deletions in the sequence relative to the standard scheme are accommodated by skipping numbers. The two schemes place certain insertions and deletions (“indels”) at different positions, resulting in differential numbering. For instance, the Chothia numbering scheme is nearly identical to the Kabat numbering scheme, except that insertions are placed at structural positions and topologically equivalents residues do get assigned the same numbers. The Contact scheme is based on analysis of complex crystal structures and is similar in many respects to the Chothia numbering scheme. The AbM scheme is a compromise between Kabat and Chothia definitions based on that used by Oxford Molecular’s AbM antibody modeling software. The IgBLAST scheme is based on matching to germline V, D and J genes, and can be determined using National Center for Biotechnology Information (NCBI)’s IgBLAST tool.

[332] In some embodiments, Kabat numbering can be determined by known sequence rules as described in, for example, Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. In some embodiments, the Kabat numbering scheme in some aspects can include any of the following rules to designate CDRs: CDR-L1 starts at approximately residue 24 of the light chain, always has a preceding C residue, and always has a following W residue; the end of CDR-L1 is defined by a stretch of 3 residues, where the W residue can be followed by Y, L, or F, followed by Q or L; CDR-1 has a length of 10 to 17 residues; CDR-L2 always starts 16 residues after the end of CDR-L1; the two residues before CDR-L2 are I and Y but can also be V and Y, I and K, or I and F; CDR-L2 is always 7 residues long; CDR-L3 always starts 33 residues after the end of CDR-L2, always has a preceding C residue, and is strictly followed by a F-G-X-G sequence motif, where X is any amino acid; CDR-L3 has a length of 7 to 11 residues; CDR-H1 starts at approximately position 26 of the heavy chain; the first amino acid in CDR-H1 is always 9 residues after a conserved C residue; CDR-H1 is followed by an invariant W residue followed by typically V, but also can be I or A; CDR-H1 has a length of 5 to 7 residues; CDR-H2 always starts at 15 residues after the end of CDR-H1; the first residue in CDR-H2 is usually preceded by the sequence motif L-E-W-I-G but a number of variations exist; the end of CDR-H2 is defined by a motif of 3 residues - the first residue of the motif of 3 residues can be either K or R, the second residue of the motif of 3 residues can be L, I, V, F, T, or A, the third residue of the motif of 3 residues can be T, S, I, or A; CDR-H2 has a length of 16 to 19 residues; CDR-H3 always starts 33 residues after the end of CDR-H2 and is always 3 residues after a C residue - the first residue of CDR-H3 is preceded by the conserved C residue followed by two residues, which are usually A-R; the residues following CDR-H3 is strictly followed by a W-G-X-G sequence motif, where the X is any amino acid; CDR-H3 typically has a length of 3 to 25 residues; CDR-H3 can be much longer than 25 residues.

[333] In some cases, according to the Chothia numbering scheme, exact boundary positions of certain CDRs can differ based on different definitions for the CDRs (See e.g., Martin, ACR, Antibody Information: How to identify the CDRs by looking at a sequence [online] bioinf.org.uk / abs / info.html). For example, in some instances, the boundary positions for CDR-L1 according to Chothia numbering can be L26--L32 (Chothia et al., Science, 1986; 233(4765):755-8 and Chothia C. and Lesk A.M. J Mol Biol, 1987; 196(4):901-17). In some instances, the boundary positions for CDR-L1 can be L25--L32 (Al-Lazikani et al., J Mol Biol, 1997; 273(4):927-48). In some instances, the boundary positions for CDR-L2 can be L50--L52 and for CDR-L3 can be L91--L96 (Chothia et al., Science, 1986; 233(4765):755-8; Chothia C. and Lesk A.M. J Mol Biol, 1987; 196(4):901-17; and Al-Lazikani et al., J Mol Biol, 1997; 273(4):927-48). In some instances, the boundary positions for CDR-H1 according to Chothia numbering can be H26--H32 (Chothia et al., Science, 1986; 233(4765):755-8; Chothia C. and Lesk A.M. J Mol Biol, 1987; 196(4):901-17; and Al-Lazikani et al., J Mol Biol, 1997; 273(4):927-48). In some instances, the boundary positions for CDR-H2 can be H53--H55 (Chothia et al., Science, 1986; 233(4765):755-8 and Chothia C. and Lesk A.M. J Mol Biol, 1987, 196(4):901-17); H52a--H55 (Tramontano et al., J Mol Biol, 1990, 215(1): 175-82), or H52--H56 (Al-Lazikani et al., J Mol Biol., 1997; 273(4):927-48). In some instances, the boundary positions for CDR-H3 can be H96--H101 (Chothia et al., Science, 1986; 233(4765):755-8 and Chothia C. and Lesk A.M. J Mol Biol., 1987; 196(4):901-17). In some instances, the boundary positions for CDR-H3 can be H92--H104 (Morea et al., Biophys Chem, 1997; 68(1-3): 9-16 and Morea et al., J Mol Biol., 1998; 275(2): 269-94).

[334] Table 1, below, exemplifies exemplary numbering and lists exemplary position boundaries of CDR-L1, CDR-L2, CDR-L3 and CDR-H1, CDR-H2, CDR-H3 as identified by Kabat, Chothia, AbM, and Contact schemes, respectively. For CDR-H1, residue numbering is listed using both the Kabat and Chothia numbering schemes. FRs are located between CDRs, for example, with FR-L1 located before CDR-L1, FR-L2 located between CDR-L1 and CDR-L2, FR-L3 located between CDR-L2 and CDR-L3 and so forth. It is noted that because the shown Kabat numbering scheme places insertions at H35A and H35B, the end of the Chothia CDR-H1 loop when numbered using the shown Kabat numbering convention varies between H32 and H34, depending on the length of the loop.Table 1. Boundaries of CDRs according to various numbering schemes.CDRKabat Chothia AbMContact CDR-L1 L24--L34 L24--L34 L24--L34L30--L36 CDR-L2 L50--L56 L50--L56 L50--L56L46--L55 CDR-L3 L89--L97 L89--L97 L89--L97L89--L96 CDR-H1(Kabat Numbering1) H31--H35BH26--H32…34H26--H35BH30--H35BCDR-H1(Chothia Numbering2)H31--H35H26--H32 H26--H35H30--H35 CDR-H2 H50--H65 H52--H56 H50--H58H47--H58 CDR-H3 H95--H102 H95--H102 H95--H102H93--H1011 - Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD2 - Al-Lazikani et al., J Mol Biol., 1997; 273(4):927-48).

[335] Thus, unless otherwise specified, a “CDR” or “complementary determining region,” or individual specified CDRs (e.g., CDR-H1, CDR-H2, CDR-H3), of a given antibody or region thereof, such as a variable region thereof, should be understood to encompass a (or the specific) complementary determining region as defined by any of the aforementioned schemes, or other known schemes. For example, where it is stated that a particular CDR (e.g., a CDR-H3) contains the amino acid sequence of a corresponding CDR in a given VH or VL region amino acid sequence, it is understood that such a CDR has a sequence of the corresponding CDR (e.g., CDR-H3) within the variable region, as defined by any of the aforementioned schemes, or other known schemes. In some embodiments, where it is stated that an antibody or antigen-binding fragment thereof comprises a CDR-H1, a CDR-H2, and a CDR-H3 as contained within a given VH region amino acid sequence and a CDR-L1, a CDR-L2, and a CDR-L3 as contained within a given VL region amino acid sequence, the CDRs can be defined by any of the aforementioned schemes (e.g., each CDR can be independently defined according to any one of the aforementioned schemes, or all CDRs can be defined according to a single scheme), such as Kabat, Chothia, AbM, IgBLAST, IMGT, or Contact method, or other known scheme. In some embodiments, specific CDR sequences are specified. Exemplary CDR sequences of provided antibodies or antigen binding fragments thereof are described using various numbering schemes, although it is understood that a provided antibody or antigen binding fragment thereof can include CDRs as described according to any of the other aforementioned numbering schemes or other known numbering schemes. In some embodiments, the CDRs are defined by less than six CDRs, such as four CDRs, e.g., CDR-H1, CDR-H2, CDR-H3, and CDR-L3, that include the paratope.

[336] In some embodiments, an antibody or antigen binding fragment thereof provided herein comprises CDRs in which the specific amino acids that are identified herein as the paratope are present and one or more amino acids at other positions (e.g., at up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 positions) are mutated relative to the CDRs of the antibody for which the applicable paratope was identified. In some embodiments, the VH and / or VL sequences of such an antibody or antigen binding fragment thereof have at least 80%, 85%, 90%, 95%, 97%, 98%, or 99% identity to the respective VH and VL sequences of the parent antibody (e.g., P20) for which the applicable paratope is provided herein.

[337] Likewise, unless otherwise specified, a FR or individual specified FR(s) (e.g., FR-H1, FR-H2, FR-H3, FR-H4, FR-L1, FR-L2, FR-L3, and / or FR-L4), of a given antibody or region thereof, such as a variable region thereof, should be understood to encompass a (or the specific) framework region as defined by any of the known schemes. In some instances, the scheme for identification of a particular CDR, FR, or FRs or CDRs is specified, such as the CDR as defined by the Kabat, Chothia, AbM, IgBLAST, IMGT, or Contact method, or other known schemes. In other cases, the particular amino acid sequence of a CDR or FR is given. In some embodiments, where it is stated that an antibody or antigen-binding fragment thereof comprises a FR-H1, a FR-H2, a FR-H3, and a FR-H4 as contained within a given VH region amino acid sequence and a FR-L1, a FR-L2, a FR-L3, and a FR-L4 as contained within a given VL region amino acid sequence, the FRs can be defined by any of the aforementioned schemes, such as Kabat, Chothia, AbM, IgBLAST, IMGT, or Contact method, or other known scheme.

[338] In some embodiments, the anti-IL-18Rβ antibodies or antigen-binding fragments thereof are defined by their variable region or variable domain, which refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen. In general, variable regions of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three CDRs (See, e.g., Kindt et al. Kuby Immunology, 6th ed., W.H. Freeman and Co., page 91 (2007)). In some embodiments, a single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind a particular antigen may be isolated using a VH or VL domain from an antibody that binds the antigen to screen a library of complementary VL or VH domains, respectively. See, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991).

[339] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment thereof. In some embodiments, the human antibody or antigen-binding fragment thereof comprises an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or a non-human source, e.g., mouse, that utilizes human antibody repertoires or other human antibody-encoding sequences, including human antibody libraries. Human antibodies may be prepared by administering an immunogen to a transgenic animal that has been modified to produce intact human antibodies or intact antibodies with human variable regions in response to antigenic challenge. Such animals typically contain all or a portion of the human immunoglobulin loci, which replace the endogenous immunoglobulin loci, or which are present extrachromosomally or integrated randomly into the animal’s chromosomes. In such transgenic animals, the endogenous immunoglobulin loci have generally been inactivated. Human antibodies also may be derived from human antibody libraries, including phage display and cell-free libraries, containing antibody-encoding sequences derived from a human repertoire.

[340] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is a chimeric antibody or antigen-binding fragment thereof. In some embodiments, the chimeric antibody is created by fusing the variable regions of an antibody from one species (e.g., human) to the constant domain of an antibody from another species (e.g., non-human). In some embodiments, the constant domain of the chimeric antibody is from a different Ig class from an IL-18Rβ antibody described herein, including IgA (including subclasses IgA1 and IgA2), IgD, IgE, IgG (including subclasses IgG1, IgG2, IgG3, and IgG4), and IgM. In some embodiments, the constant domain of the chimeric antibody comprises CH2 and CH3 domains from one or more of the different Ig classes.

[341] Among the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof are antibody fragments. Typically, an antigen binding fragment comprises all CDRs of a variable heavy chain (VH) and variable light chain (VL) sequence from antibodies and fragments thereof that bind IL-18Rβ set forth herein. However, in some embodiments, an antigen-binding fragment comprises less than all six CDRs, such as CDR-H1, CDR-H2, CDR-H3, and CDR-L3, from antibodies and fragments thereof that bind IL-18Rβ set forth herein. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof is an antigen-binding fragment selected from the group consisting of Fv, Fab, Fab’, Fab’-SH, F(ab’)2; diabodies; linear antibodies; heavy chain variable (VH) regions, single-chain antibody molecules such as scFvs and single-domain antibodies comprising only the VH region; and multi-specific antibodies formed from antibody fragments. In some embodiments, the antigen-binding fragment is a Fab fragment. In particular embodiments, the antibodies are single-chain antibody fragments comprising a heavy chain variable (VH) region and / or a light chain variable (VL) region, such as scFvs.

[342] Antibody fragments can be made by various techniques, including but not limited to proteolytic digestion of an intact antibody as well as production by recombinant host cells. In some embodiments, the antibodies are recombinantly-produced fragments, such as fragments comprising arrangements that do not occur naturally, such as those with two or more antibody regions or chains joined by synthetic linkers, e.g., peptide linkers, and / or that are may not be produced by enzyme digestion of a naturally-occurring intact antibody. In some aspects, the antibody fragments are scFvs.

[343] In some embodiments, the antigen-binding fragment is a F(ab) comprising a covalent heterodimer of the VH chain and VL chain.

[344] In some embodiments, the antigen-binding fragment is an F(ab)2 comprising two F(ab) fragments.

[345] In some embodiments, the antigen-binding fragment is an Fv fragment. In some embodiments, the Fv fragment comprises a non-covalent VH::VL heterodimer. The VH:VL heterodimer comprises an antigen-binding site which retains much of the antigen recognition and binding capabilities of the native antibody molecule, but lacking the CH1 and CL domains contained within a Fab. Inbar et al. (1972) Proc. Nat. Acad. Sci. USA 69:2659-2662; Hochman et al. (1976) Biochem 15:2706-2710; and Ehrlich et al. (1980) Biochem 19:4091-4096.

[346] In certain embodiments, the antibody or antigen-binding fragment thereof is a single chain Fv (scFv) antibody. In some embodiments, the scFv comprising the VH region and VL region of any of the embodiments disclosed herein. In some embodiments, the scFv comprises one or more linkers joining two antibody domains or regions, such as a VH region and a VL region. The linker typically is a peptide linker, e.g., a flexible and / or soluble peptide linker. In some embodiments, the linker is rich in glycine and serine and / or, in some cases, threonine. In some embodiments, the linker further comprises charged residues such as lysine and / or glutamate, which can improve solubility. In some embodiments, the linker further comprises one or more proline.

[347] ScFv antibodies may be prepared using standard molecular biology techniques following the teachings of the present application. An scFv polypeptide is a covalently linked VH::VL heterodimer which is expressed from a gene fusion including VH- and VL-encoding genes linked by a peptide-encoding linker. Huston et al. (1988) Proc. Nat. Acad. Sci. USA 85(16):5879-5883. A number of methods have been described to discern chemical structures for converting the naturally aggregated—but chemically separated—light and heavy polypeptide chains from an antibody V region into an scFv molecule which will fold into a three dimensional structure substantially similar to the structure of an antigen-binding site. See, e.g., U.S. Pat. Nos. 5,091,513 and 5,132,405, to Huston et al.; and U.S. Pat. No. 4,946,778, to Ladner et al.

[348] In certain embodiments, the antibodies described herein may be provided in the form of a UniBody®. A UniBody® is an IgG4 antibody with the hinge region removed (see GenMab Utrecht, The Netherlands; see also, e.g., US20090226421). This antibody technology creates a stable, smaller antibody format with an anticipated longer therapeutic window than current small antibody formats. IgG4 antibodies are considered inert and thus do not interact with the immune system. Fully human IgG4 antibodies may be modified by eliminating the hinge region of the antibody to obtain half-molecule fragments having distinct stability properties relative to the corresponding intact IgG4 (GenMab, Utrecht). Halving the IgG4 molecule leaves only one area on the UniBody® that can bind to cognate antigens (e.g., disease targets) and the UniBody® therefore binds univalently to only one site on target cells. For certain cancer cell surface antigens, this univalent binding may not stimulate the cancer cells to grow as may be seen using bivalent antibodies having the same antigen specificity, and hence UniBody® technology may afford treatment options for some types of cancer that may be refractory to treatment with conventional antibodies. The small size of the UniBody® can be a great benefit when treating some forms of cancer, allowing for better distribution of the molecule over larger solid tumors and potentially increasing efficacy.

[349] In certain embodiments, the antibodies or antigen-binding fragments thereof of the present disclosure may be “non-naturally occurring” antibodies. Non-naturally occurring antibodies can refer to antibodies that comprise one or more amino acid modifications, such that the resultant antibody is substantially non-naturally occurring (e.g., does not exists in nature). These amino acid modifications can include point mutations, wherein a naturally occurring amino acid is substituted for another naturally occurring amino acid. In some embodiments, the amino acid modifications can include point mutations wherein a non-naturally occurring amino acid is substituted for a naturally occurring amino acid. Non-naturally occurring antibodies can also refer to antibodies that are conjugated to a heterologous protein or compound, such as a detectable marker.

[350] Among the provided antibodies or antigen-binding fragments thereof are monoclonal antibodies, including monoclonal antibody fragments. A monoclonal antibody may be made by a variety of techniques, including but not limited to generation from a hybridoma, recombinant DNA methods, phage-display and other antibody display methods.

[351] In some aspects, the antibody or the antigen-binding fragments of the antibody is isolated.

[352] The present disclosure contemplates variants of any of the antibodies disclosed herein, including any variants as disclosed herein that comprise any modifications as described herein.

[353] Tables E12A and E16A provide the SEQ ID NOs: of exemplary provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a VH region that comprises the CDR-H1, the CDR-H2, and the CDR-H3 sequence, and a VL region that comprises the CDR-L3 sequence, as set forth in the SEQ ID NOs: listed in any row of Table E12A or E16A(by any of the listed numbering schemes, such as Kabat). In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a VH region that comprises the CDR-H1, the CDR-H2, and the CDR-H3 sequence, and a VL region that comprises the CDR-L1, the CDR-L2, and the CDR-L3 sequence, as set forth in the SEQ ID NOs: listed in any row of Table E12A or E16A(by any of the listed numbering schemes, such as, e.g., Kabat). In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a VH region sequence and a VL region sequence set forth in the SEQ ID NOs: listed in any row of Table E12A or E16A. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a VH region amino acid sequence and a VL region amino acid sequence that has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the respective VH region sequence and VL region sequence set forth in the SEQ ID NOs: listed in any row of Table E12A or E16A. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a VH region sequence and a VL region sequence set forth in the SEQ ID NOs: listed in any row of Table E12A or E16A. B. Exemplary Features

[354] In some aspects, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof have one or more specified structural and / or functional features that provide advantageous technical effects, such as high affinity binding to human and cynomolgus monkey IL-18Rβ; potency, for instance, in inhibition of IFNg production; pH-independent binding; low polyreactivity; stability; blocking of IL-18Rβ interaction with the IL-18 / IL-18Rα complex; a low immunogenicity risk; and being human.

[355] In some embodiments, the provided antibodies or antigen-binding fragment thereof specifically bind to an IL-18Rβ protein. In some embodiments, the provided antibodies and antigen-binding fragments thereof specifically bind to human IL-18Rβ. In some embodiments, the provided antibodies and antigen-binding fragments thereof specifically bind to human IL-18Rβ and cynomolgus monkey IL-18Rβ. In some embodiments, the human IL-18Rβ comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 126. Methods to determine such specific or preferential binding are also well known in the art, e.g., an immunoassay. Antibodies or antigen-binding fragments thereof that exhibit cross-reactive binding to both human IL-18Rβ and cynomolgus monkey IL-18Rβ are advantageous because it allows for testing the same antibody or antigen-binding fragment thereof in preclinical animal studies (using cynomolgus monkeys) that will later be used in humans, such as in the clinic for human studies. In other words, a surrogate antibody or antigen-binding fragment thereof would not be necessary when the antibody or antigen-binding fragment thereof of interest for use in humans binds to both human IL-18Rβ and cynomolgus monkey IL-18Rβ.

[356] In some embodiments, the provided antibodies or antigen-binding fragment thereof exhibits allosteric blocking of IL-18Rβ interacting with the IL-18 / IL-18Rα complex. Without being bound to a theory, in some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof, such as those that comprise a CDR-H1, CDR-H2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 24; or a CDR-H1, CDR-H2, and CDR-3 comprising SEQ ID NOs: 8, 9, and 10, and a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 23, and 24, respectively, exhibit allosteric blocking of IL-18Rβ interacting with the IL-18 / IL-18Rα complex.

[357] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof, such as those that comprise a CDR-H1, CDR-H2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 24; or a CDR-H1, CDR-H2, and CDR-3 comprising SEQ ID NOs: 8, 9, and 10, and a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 23, and 24, respectively, binds to an epitope of human IL-18Rβ that comprises, consists essentially of, or consists of residues 242-248, 279, 281, 282, 312, 342, and 343 of human IL-18Rβ, with residue numbering corresponding to the amino acid sequence of SEQ ID NO: 126. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof, such as those that comprise a CDR-H1, CDR-H2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 24; or a CDR-H1, CDR-H2, and CDR-3 comprising SEQ ID NOs: 8, 9, and 10, and a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 23, and 24, respectively, binds to an epitope of human IL-18Rβ that comprises, consists essentially of, or consists of residues 242-248, Phe 279, Arg 281, Val 282, Leu 312, Ser 342, and Ile 343 of human IL-18Rβ, wherein numbering of the residues corresponds to the numbering in SEQ ID NO:126. In some embodiments, the human IL-18Rβ comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 126 or an isoform thereof. Isoforms of the human IL-18Rβ sequence include, for example, UniProt sequence O95256-1 (SEQ ID NO: 126), as well as other isoforms such as, e.g., UniProt sequences O95256-2, O95256-3, and O95256-4. In some embodiments, the human IL-18Rβ comprises, consists essentially of, or consists of the mature extracellular domain of a human IL-18Rβ or a domain of human IL-18 Rβ corresponding to amino acid residues 20 to 356 of SEQ ID NO: 126. In some embodiments, the human IL-18Rβ comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 126.

[358] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a paratope disclosed herein. In some embodiments, the paratope of the anti-IL-18Rβ antibody or antigen-binding fragment thereof includes heavy chain CDR1 residues Asn 31, Tyr 32, and Tyr 33; heavy chain CDR2 residues Tyr 50, Phe 52, Tyr 53, Ser 54, Thr 56, and Asn 58; heavy chain CDR3 residues Asp 98, Val 99, Gly 100, Ile 101, Ala 102, Ala 103, Asn 105, Tyr 107, and Tyr 109; and light chain CDR3 residues Phe 91, Tyr 94, and Ile 96. In some such embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof comprises a CDR-H1, CDR-H2, and CDR-3 comprising the amino acid sequences of SEQ ID NOs: 8, 9, and 10, respectively, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 24; or a CDR-H1, CDR-H2, and CDR-3 comprising SEQ ID NOs: 8, 9, and 10, and a CDR-L1, CDR-L2, and CDR-L3 comprising the amino acid sequences of SEQ ID NOs: 22, 23, and 24, respectively.

[359] In some embodiments, the provided antibodies or antigen-binding fragment thereof exhibit potency, such as potency in inhibition of IFNg production. For instance, in some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof exhibits inhibition of IFNg production. The production of IFNg following activation of the IL-18 receptor complex mediates inflammatory effects that are associated with a variety of diseases and disorders. As such, potent inhibition of IFNg production is an advantageous technical effect for an anti-IL-18Rβ antibody or antigen-binding fragment thereof to have.

[360] Assessing inhibition of IFNg production can be performed by various assays, such by stimulating human whole blood with IL-18 and / or LPS and IL-12 in the presence of the anti-IL-18Rβ antibody or antigen-binding fragment thereof or an isotype control antibody. In some embodiments, inhibition of IFNg production is assessed based on stimulating whole human blood with LPS and IL-12 in the presence of the anti-IL-18Rβ antibody or antigen-binding fragment thereof. In some embodiments, inhibition of IFNg production is assessed based on stimulating whole human blood with IL-18 and IL-12 in the presence of the anti-IL-18Rβ antibody or antigen-binding fragment thereof.

[361] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof exhibits at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% inhibition of IFNg production, e.g., in human whole blood cells or in a cell line. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof inhibits IFNg production with an IC50 at or below 5 nM, 4 nM, 3 nM, or 2 nM. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof inhibits IFNg production with an IC50 below 3 nM. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof inhibits IFNg production with an IC50 from about 0.25 nM to about 2.5 nM, or from about 0.5 nM to about 2.5 nM, or from about 1 nM to about 2 nM, optionally wherein inhibition of IFNg production is assessed based on stimulating whole human blood with LPS and IL-12 in the presence of the anti-IL-18Rβ antibody or antigen-binding fragment thereof. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof inhibits IFNg production with an IC50 from about 0.25 nM to about 5 nM, from about 1 nM to about 5 nM, from about 1 nM to about 4 nM, from about 1 nM to about 3 nM, or from about 2 nM to about 3 nM, optionally wherein inhibition of IFNg production is assessed based on stimulating whole human blood with IL-18 and IL-12 in the presence of the anti-IL-18Rβ antibody or antigen-binding fragment thereof.

[362] In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof exhibits sustained inhibition of IFN production of at least 90% for at least one week, two weeks, or three weeks in an ex vivo assay of cynomolgus monkey whole blood assay.

[363] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof exhibit pH-independent binding. This can be advantageous by allowing the anti-IL-18Rβ antibody or antigen-binding fragment thereof to specifically bind to IL-18Rβ at both physiological pH, and in more acidic environments, such as the gastrointestinal tract or tumor microenvironments. For instance, normal tissues and cells typically exhibit a physiological pH that is a more neutral pH 7.35 to 7.45, such as pH about 7.4, whereas the pH of a tumor microenvironment or the gastrointestinal tract is typically more acidic, sometimes between about pH 5.6 and 6.8, such as about pH 6.0. The ability to bind IL-18Rβ at both physiological pH and a more acidic pH would, thus, be advantageous for treating a variety of diseases and conditions, including, e.g., inflammatory bowel disease, e.g., Crohn’s disease or ulcerative colitis, and cancers.

[364] In some embodiments, the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of 0.33 to 3.33, or about 0.33 to about 3.33. In some embodiments, the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of about 0.33 to about 3.33, about 0.33 to about 3.00, about 0.33 to about 2.5, about 0.33 to about 2, about 0.33 to about 1.75, about 0.33 to about 1.5, about 0.33 to about 1.3, about 0.5 to about 3.33, about 0.5 to about 3.00, about 0.5 to about 2.5, about 0.5 to about 2, about 0.5 to about 1.75, about 0.5 to about 1.5, about 0.5 to about 1.3, about 0.8 to about 3.33, about 0.8 to about 3.00, about 0.8 to about 2.5, about 0.8 to about 2, about 0.8 to about 1.75, about 0.8 to about 1.5, or about 0.8 to about 1.3. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of 0.8 to 1.3, or about 0.8 to about 1.3. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of about 0.9 to about 1.2. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of about 1.0 to about 1.2.

[365] In some embodiments, the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of 0.2 to 1.00, or about 0.2 to about 1.00. In some embodiments, the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of about 0.2 to about 1.00, about 0.2 to about 0.8, about 0.2 to about 0.6, about 0.2 to about 0.5, about 0.25 to about 1.00, about 0.25 to about 0.8, about 0.25 to about 0.6, or about or 0.25 to about 0.5. In some embodiments, the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of about 0.25 to about 0.5. In some embodiments, the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of about 0.3 to about 0.4.

[366] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof low polyreactivity. As used herein, an antibody or antigen-binding fragment thereof that exhibits “low polyreactivity” exhibits low non-specific binding to extracellular matrix proteins. Accordingly, in some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof exhibits low non-specific binding to extracellular matrix proteins, such as by having an extracellular matrix (ECM) score of less than 6. Low polyreactivity is advantageous because it can, e.g., reduce off-target effects caused by the antibody binding to extracellular matrix proteins, for instance; and it can also reduce or avoid the negative effects that polyreactivity can have on pharmacokinetics and bioavailability of the therapeutic antibody. Polyreactivity can be assessed by, for instance, reference to an ECM score that is calculated based on an ECM ELISA assay, where the ECM score is calculated by dividing the absorbance value of an ECM-coated sample well containing the antibody or antigen-binding fragment thereof by the absorbance of an ECM-coated sample well that does not contain the antibody or antigen-binding fragment thereof. In some embodiments, an ECM score of 6 at a concentration of 1 µM antibody or antigen-binding fragment thereof is used to determine whether an antibody or antigen-binding fragment thereof has a high or low ECM score, with a high ECM score being at or higher than 6, and a low ECM score being less than 6. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof has an ECM score of less than 6, less than 5, less than 4, or less than 3.5. In some embodiments, the anti-IL-18Rβ antibody or antigen-binding fragment thereof has an ECM score of less than 4.

[367] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof are capable of binding IL-18Rβ, such as human IL-18Rβ, with at least a certain affinity, as measured by any of a number of known methods. In some embodiments, the affinity is represented by an equilibrium dissociation constant (KD).

[368] A variety of assays are known for assessing binding affinity, equilibrium dissociation constant (KD), equilibrium association constant (KA), EC50, on-rate (association rate constant; kon or ka; units of 1 / Ms or M-1s-1) and the off-rate (dissociation rate constant; koff or kd; units of 1 / s or s-1) and / or determining whether a binding molecule (e.g., an antibody or fragment thereof) specifically binds to a particular ligand (e.g., an antigen, such as an IL-18Rβ protein). One can determine the binding affinity of a binding molecule, e.g., an anti-IL-18Rβ antibodies or antigen-binding fragments thereof, by using any of a number of binding assays that are well known. For example, in some embodiments, a BIAcore® instrument can be used to determine the binding kinetics and constants of a complex between two proteins (e.g., an anti- IL-18Rβ antibody or antigen-binding fragment thereof, and an antigen, such as an IL-18Rβ protein), using surface plasmon resonance (SPR) analysis (see, e.g., Scatchard et al., Ann. N.Y. Acad. Sci. 51:660, 1949; Wilson, Science 295:2103, 2002; Wolff et al., Cancer Res. 53:2560, 1993; and U.S. Patent Nos. 5,283,173, 5,468,614, or the equivalent).

[369] SPR measures changes in the concentration of molecules at a sensor surface as molecules bind to or dissociate from the surface. The change in the SPR signal is directly proportional to the change in mass concentration close to the surface, thereby allowing measurement of binding kinetics between two molecules. The dissociation rate constant (koff or kd), the association rate constant (kon or ka) and / or equilibrium dissociation constant (KD) and / or equilibrium association constant (KA) for the complex can be determined by monitoring changes in the refractive index with respect to time as buffer is passed over the chip. Other suitable assays for measuring the binding of one protein to another include, for example, immunoassays such as enzyme linked immunosorbent assays (ELISA) and radioimmunoassays (RIA), or determination of binding by monitoring the change in the spectroscopic or optical properties of the proteins through fluorescence, UV absorption, circular dichroism, or nuclear magnetic resonance (NMR). Other exemplary assays include, but are not limited to, Western blot, ELISA, analytical ultracentrifugation, spectroscopy, flow cytometry, sequencing, genetic reporter assays, flow cytometry, and other methods for detection of expressed nucleic acids or binding of proteins.

[370] In some binding can be determined under conditions that mimic those that exist in natural environments in the body of a subject. For instance, the pH of a tumor microenvironment or the gastrointestinal tract is typically more acidic, sometimes between about pH 5.6 and 6.8, such as about pH 6.0. In contrast, physiological pH is a more neutral pH 7.35 to 7.45, such as pH about 7.4 and more closely mimics the environment of normal tissues or cells in the blood.

[371] In some embodiments, the antibody or antigen-binding fragment thereof binds to human IL-18Rβ at pH 7.4 with an equilibrium dissociation constant (KD) that is about or less than about 10 nM, about or less than about 5 nM, about or less than about 4 nM, about or less than about 3nM, about or less than about 2 nM, about or less than about 1.5 nM, about or less than about 1.4 nM, about or less than about 1.3 nM, about or less than about 1.2 nM, about or less than about 1.1 nM, or about or less than about 1.0 nM. In some embodiments, the antibody or antigen-binding fragment thereof binds to human IL-18Rβ at pH 7.4 with a KD that is, is about, is less than, or is less than about 1.3 nM. In some embodiments, the antibody or antigen-binding fragment thereof binds to human IL-18Rβ at pH 7.4 with a KD that is or is about 0.8 nM, 0.9 nM, 1.0 nM, 1.1 nM, 1.2 nM, or 1.3 nM. In some embodiments, the antibody or antigen-binding fragment thereof binds to human IL-18Rβ at pH 7.4 with a KD that is or is about 1 nM.

[372] In some embodiments, the antibody or antigen-binding fragment thereof binds to cynomolgus IL-18Rβ at pH 7.4 with an equilibrium dissociation constant (KD) that is about or less than about 10 nM, about or less than about 5 nM, about or less than about 4 nM, about or less than about 3nM, about or less than about 2 nM, or about or less than about 1.5 nM. In some embodiments, the antibody or antigen-binding fragment thereof binds to cynomolgus IL-18Rβ at pH 7.4 with a KD that is, is about, less than, or less than about 2 nM. In some embodiments, the antibody or antigen-binding fragment thereof binds to cynomolgus IL-18Rβ at pH 7.4 with a KD that is or is about 1 nM, 1.1 nM, 1.2 nM, 1.3 nM, 1.4 nM, 1.5 nM, 1.6 nM, or 1.7 nM. In some embodiments, the antibody or antigen-binding fragment thereof binds to cynomolgus IL-18Rβ at pH 7.4 with a KD that is or is about 1.3 nM.

[373] In some embodiments, the antibody or antigen-binding fragment thereof binds to human IL-18Rβ at pH 7.4 with a KD that is, is about, less than, or less than about 1.3 nM, and binds to cynomolgus IL-18Rβ at pH 7.4 with a KD that is, is about, less than, or less than about 2 nM.

[374] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof exhibit a low immunogenicity risk, e.g., a low immunogenicity risk when administered to human subjects. Immunogenicity risk can be assessed by, for instance, determining whether a candidate therapeutic, e.g., an antibody or antigen-binding fragment thereof, contains a functional T cell epitope(s) based on the candidate therapeutic’s ability to stimulate antigen-specific CD4+ T cells in vitro. A low immunogenicity risk, e.g., in human subjects, for an antibody or antigen-binding fragment thereof is advantageous because it reduces the likelihood that the administered antibody or antigen-binding fragment thereof would trigger an unwanted immune response against the antibody or antigen-binding fragment thereof itself.

[375] Typically, protein therapeutics that induce less than a 20% response in donors are considered to have low immunogenicity risk. In some embodiments, the antibody or antigen-binding fragment thereof exhibits a low immunogenicity risk that is characterized by less than a 20% response in donors.

[376] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof are human antibodies. An antibody or antigen-binding fragment thereof that is human typically exhibits a lower immunogenicity risk than humanized antibodies, thereby contributing to a low immunogenicity risk.

[377] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof exhibit low surface hydrophobicity. Surface hydrophobicity can be assessed, for instance, by hydrophobic interaction chromatography (HIC) to determine a HIC retention time. HIC is an assay that can be used to quantify the hydrophobicity of an antibody. Slower retention times in an HIC assay are associated with, e.g., a tendency for the antibody to precipitate. In some embodiments, the HIC retention time is less than 13 minutes, less than 12 minutes, or less than 11 minutes. In some embodiments, a HIC retention time of 11 min is used as a cutoff for determining whether an antibody or antigen-binding fragment thereof exhibits low surface hydrophobicity, since ~75% of 48 clinically approved monoclonal antibodies were found in Example 2 to have an HIC retention time of lower than 11 minutes. Accordingly, in some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof exhibit low surface hydrophobicity, as determined by having a HIC retention time of less than 11 minutes.

[378] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof exhibit a low self-interaction propensity. Self-interaction of a therapeutic antibody can result in undesirable effects, such as aggregation, low solubility, or high viscosity. As such, a therapeutic antibody or antigen-binding fragment thereof having a low self-interaction propensity is advantageous for the developability of the therapeutic antibody or antigen-binding fragment thereof. The self-interaction propensity of an antibody can, for instance, be measured using a clone self-interaction (CSI) using bio-layer interferometry (BLI) assay (CSI-BLI assay), such as described in Sun et al. (2013) MAbs 2(6):838-41, or a modified version thereof. Lower CSI-BLI values are generally desirable because they indicate that the antibody has less propensity to self-interact. In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof exhibit a low self-interaction propensity, as determined by having a CSI-BLI value of less than 0.25, less than 0.20, less than 0.15, less than 0.10, less than 0.5, or less than 0.3. In some embodiments, the CSI-BLI value is about -0.1 to about 0.1. In some embodiments, the CSI-BLI value is about -0.05 to about 0.05. In some embodiments, the CSI-BLI value is about -0.05 to about 0.05, about -0.04 to about 0.03, or about -0.03 to about 0.02. In some embodiments, the CSI-BLI value is or is about -0.03, is or is about -0.02, is or is about -0.01, is or is about 0.00, is or is about 0.01, or is or is about 0.02. The self-interaction propensity of an antibody can, alternatively, be measured using a self-interaction chromatography (SIC) or cross-interaction chromatography (CIC) assay, which measure the retention time of an antibody, such as described in Sun et al., supra.

[379] In some embodiments, the provided anti-IL-18Rβ antibodies or antigen-binding fragments thereof exhibit stability, such as stability based on measurements of monomericity, charge heterogeneity, chemical stability, and / or binding to IL-18Rβ, e.g., human IL-18Rβ. In some embodiments, the provided anti-IL-18Rβ an...

Claims

1. An anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 8, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 9, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 10; andthe VL region comprises a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24.

2. An anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 34; and the VL region comprises a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 35.

3. An anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 8, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 9, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 10; andthe VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 22, a light chain complementarity determining region 2 (CDR-L2) comprising the amino acid sequence of SEQ ID NO: 36, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 24.

4. An anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 34; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 35.

5. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-4, wherein the VH region is or comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 34.

6. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-4, wherein the VH region comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 34.

7. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-4, wherein the VH region comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 34.

8. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-4, wherein the VH region comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 34.

9. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-4, wherein the VH region comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 34.

10. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-9, wherein the VL region comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 35.

11. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-9, wherein the VL region comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 35.

12. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-9, wherein the VL region comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 35.

13. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-9, wherein the VL region comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 35.

14. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-9, wherein the VL region comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 35.

15. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-14, wherein the VH region comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 34; and the VL region comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 35.

16. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-15, wherein the VH region comprises the amino acid sequence of SEQ ID NO: 34.

17. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-16, wherein the VL region comprises the amino acid sequence of SEQ ID NO: 35.

18. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-17, wherein the VH region comprises the amino acid sequence of SEQ ID NO: 34; and the VL region comprises the amino acid sequence of SEQ ID NO: 35.

19. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 1-18, wherein the antibody or antigen-binding fragment thereof is an antibody comprising a constant domain.

20. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 19, wherein the constant domain is a constant domain selected from the group consisting of an IgA1 constant domain, an IgA2 constant domain, an IgD constant domain, an IgE constant domain, an IgG1 constant domain, an IgG2 constant domain, an IgG3 constant domain, an IgG4 constant domain, and an IgM constant domain.

21. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 19 or claim 20, wherein the constant domain is an IgG1 constant domain.

22. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 19-21, wherein the antibody comprises: a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 30, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; anda light chain constant domain comprising the amino acid sequence of SEQ ID NO: 31, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31.

23. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 19-22, wherein the antibody comprises a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 30, and a light chain constant domain comprising the amino acid sequence of SEQ ID NO: 31.

24. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 19-23, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 32, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 32; anda light chain comprising the amino acid sequence of SEQ ID NO: 33, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 33.

25. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 19-24, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 32, and a light chain comprising the amino acid sequence of SEQ ID NO: 33.

26. An anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1) comprising the amino acid sequence of SEQ ID NO: 52, a heavy chain complementarity determining region 2 (CDR-H2) comprising the amino acid sequence of SEQ ID NO: 53, and a heavy chain complementarity determining region 3 (CDR-H3) comprising the amino acid sequence of SEQ ID NO: 54; andthe VL region comprises a light chain complementarity determining region 1 (CDR-L1) comprising the amino acid sequence of SEQ ID NO: 66, a light chain complementarity determining region 2 (CDR-L2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 67, and a light chain complementarity determining region 3 (CDR-L3) comprising the amino acid sequence of SEQ ID NO: 68.

27. An anti-interleukin 18 receptor beta (IL-18Rβ) antibody or antigen-binding fragment thereof, the antibody or antigen-binding fragment thereof comprising a heavy chain variable (VH) region and a light chain variable (VL) region, wherein: the VH region comprises a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2), and a heavy chain complementarity determining region 3 (CDR-H3) contained within the amino acid sequence of SEQ ID NO: 75; and the VL region comprises a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the amino acid sequence of SEQ ID NO: 76.

28. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 26 or claim 27, wherein the VH region comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 75.

29. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 26 or claim 27, wherein the VH region comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 75.

30. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 26 or claim 27, wherein the VH region comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 75.

31. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 26 or claim 27, wherein the VH region comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 75.

32. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 26 or claim 27, wherein the VH region comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 75.

33. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-32, wherein the VL region comprises an amino acid sequence having at least, or at least about 85% sequence identity to the amino acid sequence of SEQ ID NO: 76.

34. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-32, wherein the VL region comprises an amino acid sequence having at least, or at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 76.

35. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-32, wherein the VL region comprises an amino acid sequence having at least, or at least about 95% sequence identity to the amino acid sequence of SEQ ID NO: 76.

36. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-32, wherein the VL region comprises an amino acid sequence having at least, or at least about 97% sequence identity to the amino acid sequence of SEQ ID NO: 76.

37. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-32, wherein the VL region comprises an amino acid sequence having at least, or at least about 99% sequence identity to the amino acid sequence of SEQ ID NO: 76.

38. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-37, wherein the VH region comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 75; and the VL region comprises an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 76.

39. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-38, wherein the VH region comprises the amino acid sequence of SEQ ID NO: 75.

40. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-39, wherein the VL region comprises the amino acid sequence of SEQ ID NO: 76.

41. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-40, wherein the VH region comprises the amino acid sequence of SEQ ID NO: 75; and the VL region comprises the amino acid sequence of SEQ ID NO: 76.

42. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 26-41, wherein the antibody or antigen-binding fragment thereof is an antibody comprising a constant domain.

43. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 42, wherein the constant domain is a constant domain selected from the group consisting of an IgA1 constant domain, an IgA2 constant domain, an IgD constant domain, an IgE constant domain, an IgG1 constant domain, an IgG2 constant domain, an IgG3 constant domain, an IgG4 constant domain, and an IgM constant domain.

44. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 42 or claim 43, wherein the constant domain is an IgG1 constant domain.

45. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 42-44, wherein the antibody comprises: a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 30, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 30; anda light chain constant domain comprising the amino acid sequence of SEQ ID NO: 31, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 31.

46. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 42-45, wherein the antibody comprises a heavy chain constant domain comprising the amino acid sequence of SEQ ID NO: 30, and a light chain constant domain comprising the amino acid sequence of SEQ ID NO: 31.

47. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 42-46, wherein the antibody comprises: a heavy chain comprising the amino acid sequence of SEQ ID NO: 73, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 73; anda light chain comprising the amino acid sequence of SEQ ID NO: 74, or an amino acid sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the amino acid sequence of SEQ ID NO: 74.

48. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 42-47, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 73, and a light chain comprising the amino acid sequence of SEQ ID NO: 74.

49. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 1-18 and 26-41, wherein the antibody or antigen-binding fragment thereof is an antigen-binding fragment.

50. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 49, wherein the antigen-binding fragment is selected from the group consisting of a single domain antibody, a single chain antibody, an unibody, a single chain variable fragment (scFv), a Fab fragment, and a F(ab')2 fragment.

51. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-50, wherein the antibody or antigen-binding fragment thereof is recombinant.

52. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 1-51, wherein the antibody or antigen-binding fragment thereof is monoclonal.

53. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 1-52, wherein the antibody or antigen-binding fragment thereof is human.

54. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 1-25 and 49-53, wherein the antibody or antigen-binding fragment thereof binds to human IL-18Rβ at pH 7.4 with an equilibrium dissociation constant (KD) that is about 1.5 nM or is less than about 1.5 nM.

55. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 1-25 and 49-54, wherein the antibody or antigen-binding fragment thereof binds to cynomolgus IL-18Rβ at pH 7.4 with an equilibrium dissociation constant (KD) that is about 2 nM or is less than about 2 nM.

56. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 26-53, wherein the antibody or antigen-binding fragment thereof binds to human IL-18Rβ at pH 7.4 with an equilibrium dissociation constant (KD) that is, is about, is less than, or is less than about 2 nM.

57. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-25 and 49-56, wherein the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of 0.33 to 3.33, or of about 0.33 to about 3.33.

58. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 57, wherein the KD ratio is 0.8 to 1.3, or about 0.8 to about 1.3.

59. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 26-56, wherein the antibody or antigen-binding fragment thereof has a KD ratio of KD at pH 5 to KD at pH 7 of 0.25 to 1.00, or about 0.25 to about 1.00.

60. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of claim 59, wherein the KD ratio is 0.25 to 0.5, or about 0.25 to about 0.5.

61. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-25 and 49-58, wherein the anti-IL-18Rβ antibody or antigen-binding fragment thereof binds to an epitope of human IL-18Rβ that comprises, consists essentially of, or consists of residues 242-248, 279, 281, 282, 312, 342, and 343, with residue numbering corresponding to the amino acid sequence of SEQ ID NO: 126.

62. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 54-61, wherein the human IL-18Rβ comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 126.

63. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-62, wherein the anti-IL-18Rβ antibody or antigen-binding fragment thereof blocks IL-18Rβ binding to an IL-18 / IL-18Rα complex.

64. The anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-63, comprising at least one post-translational modification of the amino acid sequence, optionally wherein the at least one post-translational modification comprises a post-translational modification of a heavy chain N-terminal glutamine (Q) to a pyroglutamate.

65. A multi-specific antibody, comprising a first antigen-binding domain that binds to IL-18Rβ and a second antigen-binding domain that binds to a second antigen, wherein the first antigen-binding domain comprises the anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-64.

66. The multi-specific antibody of claim 65, that is a bispecific antibody.

67. A conjugate, comprising the anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 1-64 or the multi-specific antibody of claim 65 or claim 66, and a heterologous molecule or moiety.

68. A polynucleotide comprising a nucleic acid(s) encoding the anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 1-64, or a heavy chain or a light chain thereof.

69. A nucleic acid(s) encoding the anti-IL-18Rβ antibody or antigen-binding fragment thereof of any of claims 1-64, or a heavy chain or a light chain thereof.

70. The nucleic acid(s) of claim 69, wherein the nucleic acid(s) comprises a nucleic acid encoding a VH region comprising the nucleotide sequence of SEQ ID NO: 127 or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 127; and a nucleic acid encoding a VL region comprising the nucleotide sequence of SEQ ID NO: 128, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 128.

71. The nucleic acid(s) of claim 69 or claim 70, wherein the nucleic acid(s) comprises a nucleic acid encoding a VH region comprising the nucleotide sequence of SEQ ID NO: 127; and a nucleic acid encoding a VL region comprising the nucleotide sequence of SEQ ID NO: 128.

72. The nucleic acid(s) of any one of claims 69-71, wherein the nucleic acid(s) comprises a nucleic acid encoding a heavy chain comprising the nucleotide sequence of SEQ ID NO: 129, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 129; anda nucleic acid encoding a light chain comprising the nucleotide sequence of SEQ ID NO: 130, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 130.

73. The nucleic acid(s) of any one of claims 69-72, wherein the nucleic acid(s) comprises a nucleic acid encoding a heavy chain comprising the nucleotide sequence of SEQ ID NO: 129; anda nucleic acid encoding a light chain comprising the nucleotide sequence of SEQ ID NO: 130.

74. The nucleic acid(s) of claim 69, wherein the nucleic acid(s) comprises a nucleic acid encoding a VH region comprising the nucleotide sequence of SEQ ID NO: 131, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 131; and a nucleic acid encoding a VL region comprising the nucleotide sequence of SEQ ID NO: 132, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 132.

75. The nucleic acid(s) of claim 69 or claim 74, wherein the nucleic acid(s) comprises a nucleic acid encoding a VH region comprising the nucleotide sequence of SEQ ID NO: 131; and a nucleic acid encoding a VL region comprising the nucleotide sequence of SEQ ID NO: 132.

76. The nucleic acid(s) of any one of claims 69, 74, and 75, wherein the nucleic acid(s) comprises a nucleic acid encoding a heavy chain comprising the nucleotide sequence of SEQ ID NO: 133, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 133; anda nucleic acid encoding a light chain comprising the nucleotide sequence of SEQ ID NO: 134, or a nucleotide sequence having at least, or at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to the nucleotide sequence of SEQ ID NO: 134.

77. The nucleic acid(s) of any one of claims 69 and 74-76, wherein the nucleic acid(s) comprises a nucleic acid encoding a heavy chain comprising the nucleotide sequence of SEQ ID NO: 133; anda nucleic acid encoding a light chain comprising the nucleotide sequence of SEQ ID NO: 134.

78. A vector, comprising the polynucleotide of claim 68 or the nucleic acid(s) of any one of claims 69-77.

79. The vector of claim 78, wherein the vector is a viral vector.

80. The vector of claim 79, wherein the viral vector is a retroviral vector or a lentiviral vector.

81. A host cell comprising the anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-64, the polynucleotide of claim 68, the nucleic acid(s) of any one of claims 69-77, or the vector of any one of claims 78-80.

82. A method of producing an antibody or antigen-binding fragment thereof comprising culturing the host cell of claim 81 under a condition that produces the antibody or antigen-binding fragment thereof.

83. The method of claim 82, further comprising recovering the antibody or antigen-binding fragment thereof produced by the host cell.

84. An antibody or antigen-binding fragment thereof produced by the method of claim 82 or claim 83.

85. A composition comprising the anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-64, the multi-specific antibody of claim 65 or claim 66, or the conjugate of claim 67.

86. The composition of claim 85, further comprising a pharmaceutically acceptable excipient.

87. A method of treatment, comprising administering the anti-IL-18Rβ antibody or antigen-binding fragment thereof of any one of claims 1-64 and 84, the multi-specific antibody of claim 65 or claim 66, the conjugate of claim 67, or the composition of claim 85 or claim 86, to a subject having a disease or disorder.

88. The method of claim 87, further comprising administering one or more additional therapeutic agents.

89. The method of claim 88, wherein the one or more additional therapeutic agents comprises, consists essentially of, or consists of an aminosalicylate, a corticosteroid, a thiopurine, a methotrexate, a tumor necrosis factor (TNF) inhibitor, an α4β7 integrin inhibitor, a TNF-α inhibitor, an IL-23 inhibitor, a dual IL-12 and IL-23 inhibitor, a tumor necrosis factor-like cytokine 1A (TL1A) inhibitor, an IL-2-CD25 fusion protein, a bispecific anti-TL1A / anti-TNF-α binding protein, an E-type prostanoid receptor 4 (EP4) agonist, a TYK2 inhibitor, a sphingosine-1-phosphate receptor (S1PR) agonist, a Janus kinase (JAK) inhibitor, an interkeukin-1 receptor associated kinase 4 (IRAK-4) inhibitor, a toll-like receptor 7 and 8 (TLR7 / 8) inhibitor, or an IL-22 inhibitor.

90. The method of claim 88 or claim 89, wherein the one or more additional therapeutic agents is administered concurrently with the anti-IL-18Rβ antibody or antigen-binding fragment thereof, the multi-specific antibody, the conjugate, or the composition.

91. The method of claim 88 or claim 89, wherein the one or more additional therapeutic agents is administered before or after the anti-IL-18Rβ antibody or antigen-binding fragment thereof, the multi-specific antibody, the conjugate, or the composition.

92. The method of any one of claims 87-91, wherein the disease or disorder is an immune-mediated disease, an autoimmune disease, an inflammatory disease, a cancer, or an infectious disease.

93. The method of any one of claims 87-92, wherein the disease or disorder is associated with an increase in IL-18Rβ in a biological sample of the subject as compared to a subject not having the disease or disorder.

94. The method of claim 93, wherein the biological sample is a serum sample.

95. The method of any one of claims 87-94, wherein the disease or disorder is an immune-mediated disease.

96. The method of any one of claims 87-95, wherein the disease or disorder is an inflammatory disease.

97. The method of any one of claims 87-96, wherein the disease or disorder is an inflammatory bowel disease.

98. The method of claim 97, wherein the inflammatory bowel disease is Crohn’s disease.

99. The method of claim 97, wherein the inflammatory bowel disease is ulcerative colitis.

100. The method of any one of claims 87-96, wherein the disease or disorder is chronic obstructive pulmonary disease (COPD).

101. The method of any one of claims 87-95, wherein the disease or disorder is an autoimmune disease.

102. The method of any one of claims 87-95, wherein the disease or disorder is a cancer.

103. The method of any one of claims 87-95, wherein the disease or disorder is an infectious disease.

104. The method of any one of claims 87-95, wherein the disease or disorder is inflammatory bowel disease, chronic obstructive pulmonary disease (COPD), type 1 diabetes, type 2 diabetes, liver disease, organ transplant rejection, multiple sclerosis, arthritis, psoriasis, heart disease, macrophage activation syndrome (MAS), adult-onset Still’s disease (AOSD), hemophagocytic lymphohistiocytosis (HLH), dry eye disease (DED), cytokine release syndrome (CRS), systemic inflammatory response syndrome SIRS), autoinflammation with infantile enterocolitis (AIFEC), XIAP deficiency, NLRC4 gain-of-function mutation, sarcoidosis, atopic dermatitis, Behçet’s disease, systemic lupus erythematosus (SLE), acute coronary syndrome, allergies, amyotrophic lateral sclerosis (ALS), asthma, Celiac disease, or age-related macular degeneration (AMD), osteoporosis, Parkinson’s disease, Grave’s disease, Hashimoto’s thyroiditis, Addison’s disease, dermatomyositis, myasthenia gravis, pernicious anemia, Sjogren syndrome, vasculitis, uveitis, sepsis, atherosclerosis, ankylosing spondylitis, acute respiratory syndrome coronavirus (SARS-CoV), or acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

105. The method of claim 104, wherein: the inflammatory bowel disease is Crohn’s disease or ulcerative colitis; the arthritis is rheumatoid arthritis, psoriatic arthritis, idiopathic arthritis, or giant cell arthritis; the psoriasis is plaque psoriasis; the organ transplant rejection is a kidney transplant rejection; the heart disease is ischemic heart disease; the MAS is infantile MAS; or the sarcoidosis is pulmonary sarcoidosis.

106. The method of claim 105, wherein: the rheumatoid arthritis is juvenile rheumatoid arthritis; or the idiopathic arthritis is juvenile idiopathic arthritis.

107. The method of any one of claims 87-106, wherein the subject is a human.

108. Use of a composition of claim 85 or claim 86 for the manufacture of a medicament for treatment of a disease or disorder.

109. Use of a composition of claim 85 or claim 86 for treatment of a disease or disorder.

110. A composition of claim 85 or claim 86 for use in treatment of a disease or disorder.

111. The use of claim 108 or claim 109 or the composition for use of claim 110, wherein the treatment of the disease or disorder further comprises administering one or more additional therapeutic agents.

112. The use of any one of claims 108, 109, and 111, or the composition for use of claim 110 or claim 111, wherein the one or more additional therapeutic agents comprises, consists essentially of, or consists of an aminosalicylate, a corticosteroid, a thiopurine, a methotrexate, a tumor necrosis factor (TNF) inhibitor, an α4β7 integrin inhibitor, a TNF-α inhibitor, an IL-23 inhibitor, a dual IL-12 and IL-23 inhibitor, a tumor necrosis factor-like cytokine 1A (TL1A) inhibitor, an IL-2-CD25 fusion protein, a bispecific anti-TL1A / anti-TNF-α binding protein, an E-type prostanoid receptor 4 (EP4) agonist, a TYK2 inhibitor, a sphingosine-1-phosphate receptor (S1PR) agonist, a Janus kinase (JAK) inhibitor, an interkeukin-1 receptor associated kinase 4 (IRAK-4) inhibitor, a toll-like receptor 7 and 8 (TLR7 / 8) inhibitor, or an IL-22 inhibitor.

113. The use of any one of claims 108, 109, 111, and 112, or the composition for use of any one of claims 110-112, wherein the one or more additional therapeutic agents is to be administered concurrently with the anti-IL-18Rβ antibody or antigen-binding fragment thereof, the multi-specific antibody, the conjugate, or the composition.

114. The use of any one of claims 108, 109, 111, and 112, or the composition for use of any one of claims 110-112, wherein the one or more additional therapeutic agents is to be administered sequentially with the anti-IL-18Rβ antibody or antigen-binding fragment thereof, the multi-specific antibody, the conjugate, or the composition.

115. The use of any one of claims 108, 109, and 111-114, or the composition for use of any one of claims 110-114, wherein the disease or disorder is an immune-mediated disease, an autoimmune disease, an inflammatory disease, a cancer, or an infectious disease.

116. The use of any one of claims 108, 109, and 111-115, or the composition for use of any one of claims 110-115, wherein the disease or disorder is an immune-mediated disease.

117. The use of any one of claims 108, 109, and 111-116, or the composition for use of any one of claims 110-116, wherein the disease or disorder is an inflammatory disease.

118. The use of any one of claims 108, 109, and 111-117, or the composition for use of any one of claims 110-117, wherein the disease or disorder is an inflammatory bowel disease.

119. The use or composition for use of claim 118, wherein the inflammatory bowel disease is Crohn’s disease.

120. The use or composition for use of claim 118, wherein the inflammatory bowel disease is ulcerative colitis.

121. The use of any one of claims 108, 109, and 111-117, or the composition for use of any one of claims 110-117, wherein the disease or disorder is chronic obstructive pulmonary disease (COPD).

122. The use of any one of claims 108, 109, and 111-116, or the composition for use of any one of claims 110-116, wherein the disease or disorder is an autoimmune disease.

123. The use of any one of claims 108, 109, and 111-116, or the composition for use of any one of claims 110-116, wherein the disease or disorder is a cancer.

124. The use of any one of claims 108, 109, and 111-116, or the composition for use of any one of claims 110-116, wherein the disease or disorder is an infectious disease.

125. The use of any one of claims 108, 109, and 111-116, or the composition for use of any one of claims 110-116, wherein the disease or disorder is inflammatory bowel disease, allergy, chronic obstructive pulmonary disease (COPD), type 1 diabetes, type 2 diabetes, liver disease, organ transplant rejection, multiple sclerosis, arthritis, psoriasis, heart disease, macrophage activation syndrome (MAS), adult-onset Still’s disease (AOSD), hemophagocytic lymphohistiocytosis (HLH), dry eye disease (DED), cytokine release syndrome (CRS), systemic inflammatory response syndrome SIRS), autoinflammation with infantile enterocolitis (AIFEC), XIAP deficiency, NLRC4 gain-of-function mutation, sarcoidosis, atopic dermatitis, Behçet’s disease, systemic lupus erythematosus (SLE), acute coronary syndrome, allergies, amyotrophic lateral sclerosis (ALS), asthma, Celiac disease, or age-related macular degeneration (AMD), osteoporosis, Parkinson’s disease, Grave’s disease, Hashimoto’s thyroiditis, Addison’s disease, dermatomyositis, myasthenia gravis, pernicious anemia, Sjogren syndrome, vasculitis, uveitis, sepsis, atherosclerosis, ankylosing spondylitis, acute respiratory syndrome coronavirus (SARS-CoV), or acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

126. The use or composition for use of claim 125, wherein: the inflammatory bowel disease is Crohn’s disease or ulcerative colitis; the arthritis is rheumatoid arthritis, psoriatic arthritis, idiopathic arthritis, or giant cell arthritis; the psoriasis is plaque psoriasis; the organ transplant rejection is a kidney transplant rejection; the heart disease is ischemic heart disease; the MAS is infantile MAS; or the sarcoidosis is pulmonary sarcoidosis.

127. The use or composition for use of claim 126, wherein: the rheumatoid arthritis is juvenile rheumatoid arthritis; or the idiopathic arthritis is juvenile idiopathic arthritis. AbstractProvided are novel antibodies and antigen-binding fragments thereof that bind interleukin-18 receptor beta (IL-18Rβ), along with conjugates thereof, nucleic acids encoding the same, compositions comprising the same, and methods of producing and using the same, including in the treatment of various diseases and conditions, such as inflammatory bowel disease, and other immune-mediated diseases, autoimmune diseases, inflammatory diseases, cancers, and infectious diseases.  

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